Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

Impact of coronary hyperemia on collateral flow correction of coronary microvascular resistance indices.

Recently, a novel method to estimate wedge pressure (Pw)-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-corrected HMR.NEW & NOTEWORTHY The following are what is known: 1) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Treatment stability with bonded versus vacuum-formed retainers after 12 months: A randomized clinical trial.

OBJECTIVE: To compare the clinical effectiveness of V-bend bonded retainers (BR) versus vacuum-formed retainers (VFR) regarding their capacity to maintain treatment stability and survival rates after 12 months. MATERIALS AND METHODS: Patients finishing orthodontic treatment were randomly allocated into two groups. The BR group received maxillary and mandibular BRs in the lingual surfaces of the anterior teeth. The VFR group received VFRs right after fixed appliances removal. The patients were evaluated at four time-points: at fixed appliances removal (T0), after 3 (T1), 6 (T2) and 12 months (T3). In each time-point digital models were obtained and analysed with the OrthoAnalyzer™ software. Treatment stability based on occlusal outcomes and retainers' survival rates were evaluated. Intergroup comparisons were performed using Mann-Whitney U-tests. The Kaplan-Meier survival plot and the log-rank test were employed to assess the retainers' survival. RESULTS: Both BR and VFR groups included 25 patients. The groups were comparable regarding their baseline characteristics. Up to 6 months, both retainers were equally effective; however, after 12 months, BRs were more effective in maintaining the incisors' alignment in the maxilla and the mandible compared to the VFRs. No differences were noticed in the intercanine and intermolar widths, overjet and overbite. There were no differences regarding the retainers' survivability in both arches. CONCLUSIONS: BRs were more effective in maintaining the alignment of the incisors in the maxilla and mandible compared to VFRs after 12 months. Both retainers presented the same survival rates after the same period.

Treatment of Class II malocclusion with 2-maxillary premolar extractions: Monthly vs biweekly appointments, which is more efficient?

INTRODUCTION: This study compared whether there is a difference in treatment time (TT) and efficiency when appointments are held once a month or at 2-week intervals in patients with Class II malocclusion treated with 2-premolar extractions METHODS: The patients of this retrospective sample were treated with the same orthodontic mechanics and divided into 2 groups according to frequencies of orthodontic appointments. Group 1 consisted of 18 patients (10 males, 8 females), with an initial mean age of 14.38 ± 1.38 years and appointments once a month. Group 2 consisted of 19 patients (9 males, 10 females), with an initial mean age of 14.12 ± 1.38 years and biweekly appointments. Edgewise fixed appliances with a slot size of 0.022 × 0.028 mm were used, and the anterior teeth were retracted en-masse with a rectangular wire and elastic chains. The Peer Assessment Rating and Objective Grading System indexes were measured in the dental models at the beginning and the end of treatment. Efficiency was assessed by dividing the percentage of improvement of each occlusal index concerning the multiplication of TT and the number of appointments. RESULTS: Both groups presented similar Peer Assessment Rating and Objective Grading System indexes at the end of treatment. Groups 1 and 2 presented different TTs (28.06 and 22.05 months, respectively); however, there were no differences regarding the efficiency of both protocols. CONCLUSIONS: Patients with Class II malocclusion treated with 2-maxillary premolars had significantly shorter treatment times when seen on biweekly appointments than those with monthly appointments; however, there was no difference in efficiency between protocols.

Impact of symptom duration and mechanical circulatory support on prognosis in cardiogenic shock complicating acute myocardial infarction.

BACKGROUND: Mortality rates in patients with cardiogenic shock complicating acute myocardial infarction (AMICS) remain high despite advancements in AMI care. Our study aimed to investigate the impact of prehospital symptom duration on the prognosis of AMICS patients and those receiving mechanical circulatory support (MCS). METHODS AND RESULTS: We conducted a retrospective cohort study with data registered in the Netherlands Heart Registration. A total of 1,363 patients with AMICS who underwent percutaneous coronary intervention between 2017 and 2021 were included. Patients presenting after out-of-hospital cardiac arrest were excluded. Most patients were male (68%), with a median age of 69 years (IQR 61-77), predominantly presenting with ST-elevation myocardial infarction (86%). The overall 30-day mortality was 32%. Longer prehospital symptom duration was associated with a higher 30-day mortality with the following rates: < 3 h, 26%; 3-6 h, 29%; 6-24 h, 36%; ≥ 24 h, 46%; p < 0.001. In a subpopulation of AMICS patients with MCS (n = 332, 24%), symptom duration of > 24 h was associated with significantly higher mortality compared to symptom duration of < 24 h (59% vs 45%, p = 0.029). Multivariate analysis identified > 24 h symptom duration, age and in-hospital cardiac arrest as predictors of 30-day mortality in MCS patients. CONCLUSION: Prolonged prehospital symptom duration was associated with significantly increased 30-day mortality in patients presenting with AMICS. In AMICS patients treated with MCS, a symptom duration of > 24 h was an independent predictor of poor survival. These results emphasise the critical role of early recognition and intervention in the prognosis of AMICS patients.

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: Rationale and design of the LEGACY study.

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study.

BACKGROUND: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. METHODS: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. RESULTS: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. CONCLUSION: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.

Collateral grading systems in retrograde percutaneous coronary intervention of chronic total occlusions.

BACKGROUND: The Japanese Channel (J-Channel) score was introduced to aid in retrograde percutaneous coronary intervention (PCI) of chronic total coronary occlusions (CTOs). The predictive value of the J-Channel score has not been compared with established collateral grading systems such as the Rentrop classification and Werner grade. AIMS: To investigate the predictive value of the J-Channel score, Rentrop classification and Werner grade for successful collateral channel (CC) guidewire crossing and technical CTO PCI success. METHODS: A total of 600 prospectively recruited patients underwent CTO PCI. All grading systems were assessed under dual catheter injection. CC guidewire crossing was considered successful if the guidewire reached the distal segment of the CTO vessel through a retrograde approach. Technical CTO PCI success was defined as thrombolysis in myocardial infarction flow grade 3 and residual stenosis <30%. RESULTS: Of 600 patients, 257 (43%) underwent CTO PCI through a retrograde approach. Successful CC guidewire crossing was achieved in 208 (81%) patients. The predictive value of the J-Channel score for CC guidewire crossing (area under curve 0.743) was comparable with the Rentrop classification (0.699, p = 0.094) and superior to the Werner grade (0.663, p = 0.002). Technical CTO PCI success was reported in 232 (90%) patients. The Rentrop classification exhibited a numerically higher discriminatory ability (0.676) compared to the J-Channel score (0.664) and Werner grade (0.589). CONCLUSIONS: The J-channel score might aid in strategic collateral channel selection during retrograde CTO PCI. However, the J-Channel score, Rentrop classification, and Werner grade have limited value in predicting technical CTO PCI success.

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study.

BACKGROUND: Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. METHODS: This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·109/L), moderate (50-100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. RESULTS: Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360). CONCLUSIONS: Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Twin-block and mandibular anterior repositioning appliances effects in Class II malocclusion correction.

INTRODUCTION: The objective of this study was to compare the cephalometric changes in Class II Division 1 malocclusion patients treated with the Twin-block (TB) and the mandibular anterior repositioning appliance (MARA). METHODS: This retrospective study was performed with 132 lateral cephalograms of patients with Class II malocclusion divided into 3 groups: a TB group comprised 21 patients with mean initial and final ages of 10.59 and 11.97 years, respectively, treated for a mean period of 1.38 years; a MARA group comprised 21 patients with mean initial and final ages of 11.98 and 13.20 years, respectively, treated for a mean period of 1.22 years; and a control group included 24 subjects with untreated Class II malocclusion with mean initial and final ages of 10.55 and 12.01 years, respectively, observed for a mean period of 1.46 years. Cephalometric intergroup comparisons regarding the treatment changes (T2 - T1) were performed with the analysis of covariance, followed by Tukey tests. RESULTS: Both appliances demonstrated significant restriction of the maxilla and improvement of the maxillomandibular relationship. The MARA produced a significantly greater amount of labial tipping and protrusion of the mandibular incisors than the other groups. The TB showed significant extrusion of the mandibular incisors and molars compared with MARA and control, respectively. Both treated groups reduced the overjet and overbite. The MARA presented a significantly greater reduction in the molar relationship than the other groups. CONCLUSIONS: The appliances showed a headgear effect on the maxilla and effectively changed Class II cephalometric parameters through a combination of skeletal and dentoalveolar effects. TB showed a greater increase in LAFH. MARA promoted greater labial tipping and protrusion of the mandibular incisors.

Dentoskeletal and soft-tissue changes of class II malocclusion treatment with modified first class appliances: a prospective clinical trial.

BACKGROUND/OBJECTIVES: Intraoral distalizers are effective and conservative alternatives for Class II malocclusion treatment. However, the literature is still controversial regarding the effects of using skeletal anchorage in intraoral distalizers with different designs. The aim of this study is to compare dentoskeletal and soft-tissue changes of Class II malocclusion patients treated with three types of First Class (FC) distalizers. MATERIALS/METHODS: The sample of this prospective clinical trial included 30 consecutive patients divided into three groups: G1-FC conventionally anchored; G2-FC skeletally anchored Type 1; G3-FC skeletally anchored Type 2. Each group consisted of 10 patients. Lateral cephalograms were analyzed in two stages: at pre-treatment (T0) and after distalization (T1). The radiographs were digitized and analyzed using the software Dolphin Imaging 11.5. Comparisons of treatment changes between groups (T1-T0) were performed using one-way analysis of variance (ANOVA), followed by the Tukey test. RESULTS: Patients treated with the conventionally anchored FC showed significantly greater incisors protrusion and labial inclination, second premolars mesial inclination and mesialization than the FCs skeletally anchored. No differences were observed regarding the amount of molar distalization and molar angulation between groups. LIMITATIONS: It can be considered that the limitation of this study lies in its non-randomized design. CONCLUSIONS/IMPLICATIONS: First Class distalizers with conventional and skeletal anchorage are effective alternatives for Class II molar distalization. Distalization associated with indirect skeletal anchorage reduce the undesirable effects observed in the incisors and premolars during distalization when compared to distalization conventionally anchored.

Finite element analysis of two skeletally anchored maxillary molar distalisation methods.

OBJECTIVE: To compare two methods of maxillary molar distalisation with skeletal anchorage using finite element analysis (FEA). METHODS: Two digitised models were created: the miniscrew-anchored distaliser, which consisted of a distalisation method anchored in a buccal miniscrew between the first molar and second premolar (Model 1), and the miniscrew-anchored palatal appliance, which consisted of a distalisation method anchored in a miniscrew on the anterior region of the palate (Model 2). FEA was used to simulate both methods, assessing teeth displacements and stress concentration. RESULTS: The miniscrew-anchored distaliser showed greater buccal than distal displacement of the first molar, while the opposite was observed in the miniscrew-anchored palatal appliance. The second molar responded similarly in the transverse and anteroposterior perspectives with both appliances. Greater displacements were observed at crown level than in apical regions. Greater stress concentration was observed at the buccal and cervical regions of the crown in the miniscrew-anchored distaliser and the palatal and cervical regions in the palatal appliance. The stress progressively spread in the buccal side of the alveolar bone for the miniscrew-anchored distaliser and in the palatal root and alveolar bone for the palatal appliance. CONCLUSION: FEA assumes that both appliances would promote maxillary molar distalisation. A skeletally anchored palatal distalisation force seems to provide a greater molar bodily movement with less undesirable effects. Greater stress is expected at the crown and cervical regions during distalisation, and the stress concentration in the roots and alveolar bone depends directly on the region the force was applied.

Machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE): a modelling study of pooled datasets.

BACKGROUND: The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. METHODS: Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). FINDINGS: The PRAISE score showed an AUC of 0·82 (95% CI 0·78-0·85) in the internal validation cohort and 0·92 (0·90-0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70-0·78) in the internal validation cohort and 0·81 (0·76-0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66-0·75) in the internal validation cohort and 0·86 (0·82-0·89) in the external validation cohort for 1-year major bleeding. INTERPRETATION: A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. FUNDING: None.

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. METHODS: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. RESULTS: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. CONCLUSIONS: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Identification and treatment of the vulnerable coronary plaque.

Acute coronary syndrome mostly arises from rupture or erosion of a vulnerable plaque. Vulnerable plaques typically appear as lipid-rich plaques with a thin cap, called thin-cap fibroatheromas. Various intracoronary imaging techniques can be used to detect vulnerable plaques, such as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), each visualizing different high-risk plaque characteristics. IVUS and its post-processing techniques, such as virtual histology IVUS, can primarily be used to identify calcified and soft plaques, while OCT is also able to quantitatively measure the cap thickness. The addition of NIRS allows the exact measurement of lipid content in the plaque. Non-invasive imaging techniques to identify vulnerable plaques, such as computed tomography, are less often used but are evolving and may be of additional diagnostic use, especially when prophylactic treatments for vulnerable plaques are further established. Pharmacological treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Moreover, the implantation of a stent or scaffold for the local treatment of vulnerable plaques has been found to be safe and to stabilize high-risk plaque features. The use of drug-coated balloons to treat vulnerable plaques is the subject of ongoing research. Future studies should focus on non-invasive imaging techniques to adequately identify vulnerable plaques and further randomized clinical studies are necessary to find the most appropriate treatment strategy for vulnerable plaques.

Development and validation of a prediction model for early mortality after transcatheter aortic valve implantation (TAVI) based on the Netherlands Heart Registration (NHR): The TAVI-NHR risk model.

BACKGROUND: The currently available mortality prediction models (MPM) have suboptimal performance when predicting early mortality (30-days) following transcatheter aortic valve implantation (TAVI) on various external populations. We developed and validated a new TAVI-MPM based on a large number of predictors with recent data from a national heart registry. METHODS: We included all TAVI-patients treated in the Netherlands between 2013 and 2018, from the Netherlands Heart Registration. We used logistic-regression analysis based on the Akaike Information Criterion for variable selection. We multiply imputed missing values, but excluded variables with >30% missing values. For internal validation, we used ten-fold cross-validation. For temporal (prospective) validation, we used the 2018-data set for testing. We assessed discrimination by the c-statistic, predicted probability accuracy by the Brier score, and calibration by calibration graphs, and calibration-intercept and calibration slope. We compared our new model to the updated ACC-TAVI and IRRMA MPMs on our population. RESULTS: We included 9144 TAVI-patients. The observed early mortality was 4.0%. The final MPM had 10 variables, including: critical-preoperative state, procedure-acuteness, body surface area, serum creatinine, and diabetes-mellitus status. The median c-statistic was 0.69 (interquartile range [IQR] 0.646-0.75). The median Brier score was 0.038 (IQR 0.038-0.040). No signs of miscalibration were observed. The c-statistic's temporal-validation was 0.71 (95% confidence intervals 0.64-0.78). Our model outperformed the updated currently available MPMs ACC-TAVI and IRRMA (p value < 0.05). CONCLUSION: The new TAVI-model used additional variables and showed fair discrimination and good calibration. It outperformed the updated currently available TAVI-models on our population. The model's good calibration benefits preprocedural risk-assessment and patient counseling.

Collagenase to facilitate guidewire crossing in chronic total occlusion PCI-The Total Occlusion Study in Coronary Arteries-5 (TOSCA-5) trial.

BACKGROUND: Chronic total occlusions (CTO) are common and are associated with lower percutaneous coronary intervention (PCI) success rates, often due to failure of antegrade guidewire crossing. Local, intralesional delivery of collagenase (MZ-004) may facilitate guidewire crossing in CTO. AIMS: To evaluate the effect of MZ-004 in facilitating antegrade wire crossing in CTO angioplasty. METHODS: A total of 76 patients undergoing CTO PCI were enrolled at 13 international sites: 38 in the randomized training stage (collagenase [MZ-004] 900 or 1200 µg) and 38 in the placebo-controlled stage (MZ-004 900 or 1200 µg or placebo). Patients received the MZ-004 or identical volume saline (placebo group) in a double-blind design, injected via microcatheter directly into the proximal cap of the CTO. The following day patients underwent CTO PCI using antegrade wire techniques only. RESULTS: Patients were generally similar except for a trend for higher Japanese chronic total occlusion (J-CTO) score in the MZ-004 group (MZ-004 J-CTO score 1.9 vs. 1.4, p = 0.07). There was a numerical increase in the rates of guidewire crossing in the MZ-004 groups compared to placebo (74% vs. 63%, p = 0.52). Guidewire crossing with a soft-tip guidewire (≤1.5 g tip load) was significantly higher in the MZ-004 groups (0% in placebo, 17% in 900 µg, and 29% in 1200 µg MZ-004 group, p = 0.03). Rates of the major adverse cardiovascular event were similar between groups. CONCLUSION: Local delivery of MZ-004 into coronary CTOs appears safe and may facilitate CTO crossing, particularly with softer tipped guidewires. These data support the development of a pivotal trial to further evaluate this agent.

DEtection of ProxImal Coronary stenosis in the work-up for Transcatheter aortic valve implantation using CTA (from the DEPICT CTA collaboration).

OBJECTIVES: Computed tomography angiography (CTA) is performed routinely in the work-up for transcatheter aortic valve implantation (TAVI), and could potentially replace invasive coronary angiography (ICA) to rule out left main (LM) and proximal coronary stenosis. The objectives were to assess the diagnostic yield and accuracy of pre-TAVI CTA to detect LM and proximal coronary stenosis of ≥ 50% and ≥ 70% diameter stenosis (DS). METHODS: The DEPICT CTA database consists of individual patient data from four studies with a retrospective design that analyzed the diagnostic accuracy of pre-TAVI CTA to detect coronary stenosis, as compared with ICA. Pooled data were used to assess diagnostic accuracy to detect coronary stenosis in the left main and the three proximal coronary segments on a per-patient and a per-segment level. We included 1060 patients (mean age: 81.5 years, 42.7% male). RESULTS: On ICA, the prevalence of proximal stenosis was 29.0% (≥ 50% DS) and 15.7% (≥ 70% DS). Pre-TAVI CTA ruled out ≥ 50% DS in 51.6% of patients with a sensitivity of 96.4%, specificity of 71.2%, PPV of 57.7%, and NPV of 98.0%. For ≥ 70% DS, pre-TAVI CTA ruled out stenosis in 70.0% of patients with a sensitivity of 96.7%, specificity of 87.5%, PPV of 66.9%, and NPV of 99.0%. CONCLUSION: CTA provides high diagnostic accuracy to rule out LM and proximal coronary stenosis in patients undergoing work-up for TAVI. Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of patients, using a threshold of ≥ 50% or ≥ 70% DS, respectively. KEY POINTS: • Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of TAVI patients, using a threshold of ≥ 50% or ≥ 70% diameter stenosis. • The diagnostic accuracy of CTA to exclude proximal coronary stenosis in these patients is high, with a sensitivity of 96.4% and NPV of 98.0% for a threshold of ≥ 50%, and a sensitivity of 96.7% and NPV of 99.0% for a threshold of ≥ 70% diameter stenosis. • Atrial fibrillation and heart rate did not significantly affect sensitivity and NPV. However, a heart rate of < 70 b/min during CTA was associated with a significantly improved specificity and PPV.