Health-related quality of life one year after refractory cardiac arrest treated with conventional or extracorporeal CPR; a secondary analysis of the INCEPTION-trial.

Background: Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR. Methods: We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL. Results: A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14). Conclusion: One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.

Disease relapse in relation to lymph node sampling in lung carcinoid patients.

The predictive value of extent of per-operative lymph node (LN) sampling in relation to disease relapse in patients with pulmonary carcinoid (PC) is unknown. Furthermore, post-surgery follow-up recommendations rely on institutional retrospective studies with rather short follow-up. We aimed to address these short-comings by examining the relation between LN sampling and relapse in a population-based cohort with long-term follow-up. By combining the Dutch nation-wide pathology and cancer registries, all patients with surgically resected PC (2003-2012) were included in this analysis (last update 2020). Extent of surgical LN dissection was scored for number of LN sampled, location (hilar/mediastinal), and completeness of resection according to European Society of Thoracic Surgeons (ESTS) guidelines. Relapse free interval (RFI) was evaluated using Kaplan Meier and multivariate regression analysis. 662 patients were included. Median follow-up was 87.5 months. Relapse occurred in 10% of patients, mostly liver (51.8%) and locoregional sites (45%). Median RFI was 48.1 months (95% CI 36.8-59.4). Poor prognostic factors were atypical carcinoid, pN1/2 and R1/R2 resection. In 546 patients LN dissection data could be retrieved; at least one N2 LN was examined in 44% and completeness according to ESTS in merely 7%. In 477 cN0 patients, 5.9% had pN1 and 2.5% pN2 disease. In this population-based cohort, relapse occurred in 10% of PC patients with a median RFI of 48.1 months thereby underscoring the necessity of long-term follow-up. Extended mediastinal LN sampling was rarely performed but systematic nodal evaluation is recommended as it provides prognostic information on distant relapse.

Favorable resuscitation characteristics in patients undergoing extracorporeal cardiopulmonary resuscitation: A secondary analysis of the INCEPTION-trial.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR. Methods: We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1-2) and unfavorable or non-survivors (CPC 3-5). Results: In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors (n = 5) and non-survivors (n = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, p = 0.037), underwent more defibrillation attempts (13 vs. 6, p = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, p = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events. Conclusion: The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors.Clinical trial Registration:clinicaltrials.gov registration number NCT03101787.

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections.

Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM-VSMC network.

Building a patient-centred nationwide integrated cardiac care registry: intermediate results from the Netherlands.

This paper presents an overview of the development of an integrated patient-centred cardiac care registry spanning the initial 5 years (September 2017 to December 2022). The Netherlands Heart Registration facilitates registration committees in which mandated cardiologists and cardiothoracic surgeons structurally evaluate quality of care using real-world data. With consistent attendance rates exceeding 60%, a valuable network is supported. Over time, the completeness level of the registry has increased. Presently, four out of six quality registries show over 95% completeness in variables that are part of the quality policies of cardiology and cardiothoracic surgery societies. Notably, 93% of the centres voluntarily report outcomes related to open heart surgery and (trans)catheter interventions publicly. Moreover, outcomes after implantable cardioverter-defibrillator and pacemaker procedures are transparently reported by 26 centres. Multiple innovation projects have been initiated by the committees, signalling a shift from publishing outcomes transparently to collaborative efforts in sharing healthcare processes and investigating improvement initiatives. The next steps will focus on the entire pathway of cardiac care for a specific medical condition instead of focusing solely on the outcomes of the procedures. This redirection of focus to a comprehensive assessment of the patient pathway in cardiac care ultimately aims to optimise outcomes for all patients.

Cost-effectiveness of ECPR versus CCPR in OHCA; A pre-planned, trial-based economic evaluation.

INTRODUCTION: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. METHODS: This cost-effectiveness study was part of the INCEPTION study, a multicenter, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centers in the Netherlands. We analyzed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratio's (ICER), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-treated subgroups as well as imputed productivity loss in deceased patients. RESULTS: In total 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after one year was €5,109 (95%CI -7,264-15,764). Mean QALY after one year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121,643 per additional QALY gained. The acceptability curve shows that at a willingness-to-pay threshold of €80.000, the probability of ECPR being cost-effective compared to CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-treated groups and lower probabilities of acceptance. CONCLUSION: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation.

Circulating BMP10 Levels Associate With Late Postoperative Atrial Fibrillation and Left Atrial Endomysial Fibrosis.

BACKGROUND: Serum bone morphogenetic protein 10 (BMP10) blood levels are a marker for history of atrial fibrillation (AF) and for major adverse cardiovascular events in patients with AF, including stroke, AF recurrences after catheter ablations, and mortality. The predictive value of BMP10 in patients undergoing cardiac surgery and association with morphologic properties of atrial tissues are unknown. OBJECTIVES: This study sought to study the correlation between BMP10 levels and preoperative clinical traits, occurrence of early and late postoperative atrial fibrillation (POAF), and atrial fibrosis in patients undergoing cardiac surgery. METHODS: Patients with and without preoperative AF history undergoing first cardiac surgery were included (RACE V, n = 147). Preoperative blood biomarkers were analyzed, left (n = 114) and right (n = 125) atrial appendage biopsy specimens were histologically investigated after WGA staining, and postoperative rhythm was monitored continuously with implantable loop recorders (n = 133, 2.5 years). RESULTS: Adjusted multinomial logistic regression indicated that BMP10 accurately reflected a history of persistent AF (OR: 1.24, 95% CI: 1.10-1.40, P = 0.001), similar to NT-pro-BNP. BMP10 levels were associated with increased late POAF90 occurrence after adjustment for age, sex, AF history, and early POAF occurrence (HR: 1.07 [per 0.1 ng/mL increase], 95% CI: 1.00-1.14, P = 0.041). Left atrial endomysial fibrosis (standardized ß = 0.22, P = 0.041) but not overall fibrosis (standardized Β = 0.12, P = 0.261) correlated with circulating BMP10 after adjustment for age, sex, AF history, reduced LVF, and valvular surgery indication. CONCLUSIONS: Increased BMP10 levels were associated with persistent AF history, increased late POAF incidence, and LAA endomysial fibrosis in a diverse sample of patients undergoing cardiac surgery.

Left atrial function of patients with atrial fibrillation undergoing thoracoscopic hybrid ablation.

OBJECTIVES: Thoracoscopic hybrid ablation is an effective and safe rhythm control strategy for patients with complex forms of atrial fibrillation. Its effect on left atrial function has not yet been studied. METHODS: In a retrospective single-centre analysis of patients undergoing thoracoscopic hybrid ablation, the left atrial emptying fraction was calculated using the biplane modified Simpson method in the apical 2- and 4-chamber views on transthoracic echocardiography. Left atrial strain (reservoir, conduction and contractility) was quantified using dedicated software. RESULTS: Sixty-seven patients were included (mean age 64 years, long-standing persistent atrial fibrillation in 69%, median atrial fibrillation history duration 64 months). At baseline, left atrial function and contractility were poor. The reservoir and contractile strain improved postprocedure compared to baseline [15 (standard deviation (SD): 8) and 17 (SD: 6); P = 0.013; 3 (SD: 5) and 4 (SD: 4), P = 0.008], whereas the left atrial volume indexed to the body surface area was reduced [51 ml/m2 (SD: 14) and 47 ml/m2 (SD: 18), P = 0.0024]. In patients with preoperative (long-standing) persistent atrial fibrillation and in patients with rhythm restoration, improvements in the emptying fraction, (reservoir and contractile) strain and the left ventricular ejection fraction were observed, whereas the left atrial volume decreased (P < 0.05). CONCLUSIONS: In this cohort of patients with severely diseased left atria, improvement in left atrial contractility and in the emptying fraction after thoracoscopic hybrid ablation for atrial fibrillation in patients with persistent atrial fibrillation is mainly due to rhythm restoration. Interestingly, the procedure itself also results in improved left atrial reservoir strain and reversed left atrial remodelling by reducing left atrial volume.

One-year postprocedural quality of life following mitral valve surgery: data from The Netherlands heart registration.

OBJECTIVES: The aim of surgical treatment of mitral valve disease is to reverse heart failure and to restore life expectancy and quality of life (QoL). In mitral valve surgery, QoL has not been studied extensively, especially regarding the surgical approach. The current study aimed to evaluate QoL after mitral valve surgery through full sternotomy and a minimally invasive approach (MIMVS). METHODS: All patients undergoing mitral valve surgery between 2013-2018 through sternotomy or a MIMVS approach (right anterolateral mini-thoracotomy, sternal-sparing), with or without concomitant tricuspid valve surgery, surgical ablation, or atrial septal defect closure were eligible for inclusion in this multicentre nationwide registry in the Netherlands. Quality of life was measured using the 12- and 36-item short form surveys, before surgery and postoperatively at 1 year. Independent predictors for loss of QoL were evaluated. RESULTS: 485 patients were included (full sternotomy: n = 276, and MIMVS: n = 209). Overall, patients experienced a significant increase in physical component score (56 [42-75] vs 74 [57-88], p < 0.001) and mental component score at 1-year (63 [52-74] vs 70 [59-86], p < 0.001). Baseline QoL scores and new onset of atrial arrhythmia were independently associated with a clinically relevant reduction in physical and mental QoL. CONCLUSIONS: Mitral valve surgery is associated with significant improvement in physical and mental QoL. Baseline QoL scores and new onset of atrial arrhythmia are associated with a clinically relevant reduction in postoperative QoL.

Proposal of statistical twin as a transition to full digital twin technology for cardiovascular interventions.

OBJECTIVES: We introduced statistical twin as aggregates of multiple virtual patients' data throughout the treatment at any chosen time point. The goal of this manuscript was to provide the proof of concept of statistical twin by evaluating the feasibility of detection of distinctive aggregates of patients throughout the perioperative trajectory (prerequisite for development of statistical twin). METHODS: We used a retrospective validated cohort of all comers with mitral valve disease treated (2014-2020) at a tertiary academic hospital. The end point was overall survival based on the decision of the heart team. We applied two-step cluster analysis to detect distinct aggregated virtual patients throughout the process of care. RESULTS: The cluster procedure resulted in 5 distant clusters with relatively equal numbers of patients. Effects of the treatment (surgery, transcatheter or optimal medical therapy) on survival were as follows: For optimal medical therapy, the expected survival ranged from 95% to 96% in 30 days to 58% to 75% in 10 years independent of baseline characteristics. However, for transcatheter interventions, the 5-year survival was 60-92% and was dependant on the initial characteristics of the virtual patient. Furthermore, survival following an uncomplicated operation of normal duration was higher through all observation periods. The aggregated virtual patients of cluster 5 would have a better survival rate at all times if the intervention were done by a dedicated surgeon. CONCLUSIONS: It is possible to detect distinctive aggregates of virtual patients based on baseline characteristics and to capture the impact of perioperative events and external and other factors at multiple time points throughout the postoperative phase.

Clinical Predictors of Device-Detected Atrial Fibrillation During 2.5 Years After Cardiac Surgery: Prospective RACE V Cohort.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery that is associated with late atrial fibrillation (AF) recurrences (late-POAF) and increased morbidity and long-term mortality. OBJECTIVES: This study sought to determine device-detected POAF incidence and to identify clinical variables associated with POAF, both in patients with and without preoperative AF history. METHODS: A total of 133 consecutive patients undergoing cardiac surgery were prospectively enrolled and continuously monitored with an implantable loop recorder for 2.5 years after surgery. Preoperative transthoracic echocardiography, 12-lead electrocardiogram, blood biomarkers, and clinical data were analyzed to develop prediction models for early- and late-POAF. RESULTS: In patients without preoperative AF history, early-POAF within the first 90 postoperative days occurred in 41 (47.1%) of 87 patients. Late-POAF after the first 90 postoperative days occurred in 22 (25%) of 87 patients, and 20 of these patients also had early-POAF during the first 90 days (20 of 22 [91%]). Increased right atrial minimum volume indexed for body surface area (RAVImin) and early-POAF were independently associated with late-POAF. A prediction model for late-POAF, which included RAVImin >11 mL/m2, age >65 years, and early-POAF, achieved an area under the curve of 0.82 (95% CI: 0.72-0.92). For patients with preoperative AF-history, late-POAF recurrences were frequent (22 of 33 [67%]). Increased RAVImin was independently associated with a higher incidence of late-POAF. CONCLUSIONS: In patients with and without AF history, late-POAF recurrences are frequent, including in patients undergoing surgical AF ablation. In patients with no history of AF, late-POAF might be predicted with excellent accuracy by using a combination of preoperative variables. In patients with a history of AF, signs of advanced AF substrate (eg, increased right atrial volumes) were associated with long-term AF recurrences. [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF; NCT03124576].

Prediction of poor exposure in endoscopic mitral valve surgery using computed tomography.

OBJECTIVES: In endoscopic mitral valve surgery, optimal exposure is crucial. This study aims to develop a predictive model for poor mitral valve exposure in endoscopic surgery, utilizing preoperative body profiles and computed tomography images. METHODS: We enrolled patients undergoing endoscopic mitral valve surgery with available operative video and preoperative computed tomography. The degree of valve exposure was graded into 0 (excellent), 1 (fair), 2 (poor) and 3 (very poor). Intrathoracic dimensions-anteroposterior width (chest anteroposterior) and left-to-right width (chest width) of the thorax, height of right hemi-thorax (chest height), angle between the left ventricular axis and the horizontal plane (left ventricle apex angle), heart width, level of diaphragm in midline, and vertical distance between the midline diaphragm level and the highest top of the right diaphragm (Δdiaphragm) were measured. RESULTS: Among 263 patients, mitral valve exposure was graded as 0 in 131 (49.8%), 1 in 72 (27.4%), 2 in 46 (17.5%) and 3 in 14 (5.3%). Body mass index, chest width, left ventricle apex angle, heart width and Δdiaphragm were identified as independent predictors of grades 2 and 3 exposure by stepwise logistic regression analysis, with an area under the receiver operating characteristic curve of 0.822 (P < 0.001). Univariate logistic regression for grade 3 exposure prediction revealed that Δdiaphragm had the largest area under the curve (0.826, P < 0.001). CONCLUSIONS: Poor mitral valve exposure occurred in approximately one-fourth of the endoscopic surgery series and might be predicted preoperatively using body mass index and computed tomography measurements to help determine the surgical approach.

Simulation-based training for endoscopic mitral valve repair: the impact on basic surgical skills for placement of sutures at mitral valve annulus during 2-h training workshop.

OBJECTIVES: The aim of this study was to evaluate the impact of simulation-based training on surgical skills during 2-h learning labs during surgical annual meeting. METHODS: During the 36th European Association of Cardiothoracic Surgery annual meeting a learning drylab for simulation-based training for endoscopic mitral valve repair was set up. For this purpose, a validated high-fidelity endoscopic mitral valve surgery simulator and a validated suturing map were used. The training lasted 2 h. Technical pre- and post-assessment were carried out based on time and accuracy to place a suture at the posterior mitral valve annulus. The suture had to be placed within 60 s. The suture was considered anatomically correct if it entered and exited the annulus at the designated place (on the posterior annulus) and accurate if placed within the right width (8-12 mm). RESULTS: In total, 46 participants were included in this study, of whom 18 (38%) were experienced/staff surgeons, 23 (51%) fellows and 5 (11%) residents. Before the training, 48% of the participants failed to place any suture for pre-assessment. After completing the training, 100% of the participants succeeded in placing an anatomically correct suture. There was a significant improvement in the time taken [pre-assessment mean 45 (standard deviation: 25) s vs post-assessment mean 18 (standard deviation: 12) s, P < 0.001] and the accuracy to place a suture in the mitral valve annulus after completing the training (pre-assessment 32.6% vs post-assessment 65.2%, P < 0.001). CONCLUSIONS: This study shows a significant improvement in endoscopic skills for mitral valve surgery after completing a 2-h training with a high-fidelity endoscopic mitral valve surgery simulator. This suggests that simulation trainings during scientific annual meetings are effective on surgical skills.

Extracorporeal life support in cardiac arrest: a post hoc Bayesian re-analysis of the INCEPTION trial.

AIMS: Previously, we performed the multicentre INCEPTION trial, randomizing patients with refractory out-of-hospital cardiac arrest (OHCA) to extracorporeal cardiopulmonary resuscitation (ECPR) or conventional cardiopulmonary resuscitation (CCPR). Frequentist analysis showed no statistically significant treatment effect for the primary outcome; 30-day survival with a favourable neurologic outcome (cerebral performance category score of 1-2). To facilitate a probabilistic interpretation of the results, we present a Bayesian re-analysis of the INCEPTION trial. METHODS AND RESULTS: We analysed survival with a favourable neurologic outcome at 30 days and 6 months under a minimally informative prior in the intention-to-treat population. Effect sizes are presented as absolute risk differences (ARDs) and relative risks (RRs), with 95% credible intervals (CrIs). We estimated posterior probabilities at various thresholds, including the minimal clinically important difference (MCID) (5% ARD), based on expert consensus, and performed sensitivity analyses under sceptical and literature-based priors. The mean ARD for 30-day survival with a favourable neurologic outcome was 3.6% (95% CrI -9.5-16.7%), favouring ECPR, with a median RR of 1.22 (95% CrI 0.59-2.51). The posterior probability of an MCID was 42% at 30 days and 42% at 6 months, in favour of ECPR. CONCLUSION: Bayesian re-analysis of the INCEPTION trial estimated a 42% probability of an MCID between ECPR and CCPR in refractory OHCA in terms of 30-day survival with a favourable neurologic outcome. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03101787, registered 5 April 2017).

Early extracorporeal CPR for refractory out-of-hospital cardiac arrest - A pre-planned per-protocol analysis of the INCEPTION-trial.

BACKGROUND: Evidence for extracorporeal cardiopulmonary resuscitation (CPR) in refractory out-of-hospital cardiac arrest (OHCA) remains inconclusive. Recently, the INCEPTION-trial, comparing extracorporeal with conventional CPR, found no statistically significant difference in neurologically favorable survival. Since protocol deviations were anticipated, a pre-specified per-protocol analysis was foreseen. METHODS: The per-protocol analysis of the INCEPTION trial excluded patients not meeting inclusion or exclusion criteria, amongst which time-to-cannulation of >60 minutes, and achieving a return of spontaneous circulation before hospital arrival. Crossovers were excluded as well. The primary outcome (30-day survival in a neurologically favorable condition; cerebral performance category [CPC] 1-2) was primarily analyzed under a frequentist statistical framework. In addition, Bayesian analysis under a minimally informative prior was performed. RESULTS: Eighty-one patients were included in the per-protocol analysis (extracorporeal CPR n = 33, conventional CPR n = 48). Thirty-day survival with CPC1-2 was 15% in the extracorporeal CPR group versus 9% in the conventional CPR group (adjusted OR 1.9; 95% CI 0.4-9.3; p-value 0.393). Bayesian analysis showed an 84% posterior probability of any ECPR benefit and a 61% posterior probability of a 5% absolute risk reduction for the primary outcome. CONCLUSION: A pre-planned, pre-specified per-protocol analysis of the INCEPTION-trial, found a higher survival with favorable neurological in patients undergoing ECPR versus CCPR for refractory shockable OHCA. This difference did not reach statistical significance, but results should be interpreted with care, in the light of the small remaining sample size.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

Heart Failure, Female Sex, and Atrial Fibrillation Are the Main Drivers of Human Atrial Cardiomyopathy: Results From the CATCH ME Consortium.

BACKGROUND: Atrial cardiomyopathy (atCM) is an emerging prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are hallmarks of atCM. The contribution of etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been quantified. This study aimed to evaluate the association between histological features of atCM and the clinical phenotype. METHODS AND RESULTS: We examined left atrial (LA, n=95) and right atrial (RA, n=76) appendages from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed following wheat germ agglutinin/CD31/vimentin staining. The contributions of AF, heart failure, sex, and age to histological characteristics were determined with multiple linear regression models. Persistent AF was associated with increased endomysial fibrosis (LA: +1.13±0.47 µm, P=0.038; RA: +0.94±0.38 µm, P=0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 µm, P<0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 µm, P=0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 µm, P<0.001) and extracellular matrix content (LA: +3.07±1.29%, P=0.016), and a higher capillary density (LA: +0.13±0.06, P=0.007) and size (LA: +0.46±0.22 µm, P=0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 µm, P<0.001; RA: +2.86 µm, P<0.001), extracellular matrix content (LA: +3.53%, P<0.001; RA: +6.40%, P<0.001) and fibroblast density (LA: +4.38%, P<0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 µm, P=0.008; RA: +2.58 µm, P<0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, P=0.002; RA: OR, 1.54, P=0.004), with persistent AF (LA: OR, 1.22, P=0.036) or heart failure (LA: OR, 1.62, P<0.001). Hypertrophic features were more common in men (LA: OR=1.33, P=0.002; RA: OR, 1.54, P=0.004). CONCLUSIONS: Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men.

Bayesian interpretation of non-inferiority in transcatheter versus surgical aortic valve replacement trials: a systematic review and meta-analysis.

OBJECTIVES: The concept of non-inferiority is widely adopted in randomized trials comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). However, uncertainty exists regarding the long-term outcomes of TAVR, and non-inferiority may be difficult to assess. We performed a systematic review and meta-analysis of randomized trials comparing TAVR and SAVR, with a specific emphasis on the non-inferiority margin for 5-year all-cause mortality. METHODS: A systematic search was applied to 3 electronic databases. Randomized trials comparing TAVR and SAVR were included. Bayesian methods were implemented to evaluate the posterior probability of non-inferiority at different trial non-inferiority margins under either a vague, Cauchy, or a literature-based prior. Primary outcomes were 5-year actuarial all-cause mortality, and the probability of non-inferiority at various transformed trial non-inferiority margins. Secondary outcomes were long-term survival and 1- and 2-year actuarial survival. RESULTS: Eight trials (n = 8698 patients) were included. Kaplan-Meier-derived 5-year survival was 61.6% (95% CI 59.8-63.5%) for TAVR, and 63.7% (95% CI 61.9-65.6%) for SAVR. Six trials (n = 6370 patients) reported all-cause mortality at 5-year follow-up. Under a vague prior, the posterior median relative risk for all-cause mortality of TAVR was 1.14, compared to SAVR (95% credible interval 1.06-1.22, probability of relative risk <1.00 = 0.01%, I2 = 0%). Similar results in terms of point estimate and uncertainty measures were obtained using frequentist methods. Based on the various trial non-inferiority margins, the results of the analysis suggest that non-inferiority at 5 years is no longer likely. CONCLUSIONS: It is unlikely that TAVR is still non-inferior to SAVR at 5 years in terms of all-cause mortality.

Extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest - current status.

PURPOSE OF REVIEW: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging treatment for refractory cardiac arrest. In recent years, several randomized controlled trials have been published that aimed to address the efficacy and effectiveness of ECPR for out-of-hospital cardiac arrest (OHCA). Despite the lack of high-quality evidence concerning clinical effectiveness and cost-effectiveness, ECPR is increasingly implemented throughout the world. In this review, we aim to provide an overview of the current status of ECPR for OHCA. RECENT FINDINGS: Randomized controlled trials showed diverging results, largely due to differences in selection criteria and study design. Single-center studies, performed in centers with extraordinary expertise and dedication consistently achieve a low-flow time of around 60 min, but such achievements are rarely reproduced outside these centers. Strict patient selection can improve outcome but simultaneously limits the caseload. Preliminary data suggest that outcome may also be improved by avoiding hyperoxia postresuscitation. SUMMARY: The potential of ECPR to increase survival in selected patients in highly dedicated systems seems to be proven, the question remains whether ECPR for OHCA can be widely implemented successfully and can develop into a sustainable, commonplace resource-effective treatment.

Optimal management of cardiac surgery patients using direct oral anticoagulants: recommendations for clinical practice.

OBJECTIVES: Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase. METHODS: A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting. RESULTS: When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available. CONCLUSIONS: DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.