Individual patient data meta-analysis on awake pediatric extracorporeal life support: Feasibility and safety of analgesia, sedation and respiratory support weaning, and physiotherapy.

OBJECTIVE: Awake Extracorporeal Life Support (aECLS) with active mobilization has gained consensus over time, also within the pediatric community. This individual patient data (IPD) meta-analysis summarizes available evidence on pediatric aECLS, its feasibility, and safety regarding sedation weaning, extubation, and physiotherapy. METHODS: PubMed/Medline and Cochrane Database were screened until February 2022. Articles reporting on children (≤18 years) undergoing aECLS were selected. IPD were requested, pooled in a single database, and analyzed using descriptive statistics. Primary outcome was survival to hospital discharge. Secondary outcomes included extubation during ECLS, physiotherapy performed, tracheostomy, and complications. RESULTS: Nineteen articles and 65 patients (males:n = 30/59,50.8%) were included. Age ranged from 2 days to 17 years. ECLS configurations included veno-venous (n = 42/65, 64.6%), veno-arterial (n = 18/65, 27.7%) and other ECLS settings (n = 5/65, 7.7%). Exclusive neck cannulation was performed in 51/65 (78.5%) patients. Extubation or tracheostomy during ECLS was reported in 66.2% (n = 43/65) and 27.7% (n = 18/65) of patients, respectively. Physiotherapy was reported as unspecified physical activity (n = 34/63, 54%), mobilization in bed (n = 15/63, 23.8%), ambulation (n = 14/63, 22.2%). Complications were reported in 60.3% (n = 35/58) of patients, including hemorrhagic (36.2%), mechanical (17.2%), or pulmonary (17.2%) issues, and need for reintubation (15.5%). Survival at discharge was 81.5% (n = 53/65). CONCLUSION: Awake ECLS strategy with active physiotherapy can be applied in children from neonatal age. Ambulation is also possible in selected cases. Complications related to such management were limited. Further studies on aECLS are needed to evaluate safety and efficacy of early physiotherapy and define patient selection.

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.

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].

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.

Type A aortic dissection: optimal annual case volume for surgery.

BACKGROUND AND AIMS: The current study proposes a novel volume-outcome (V-O) meta-analytical approach to determine the optimal annual hospital case volume threshold for cardiovascular interventions in need of centralization. This novel method is applied to surgery for acute type A aortic dissection (ATAAD) as an illustrative example. METHODS: A systematic search was applied to three electronic databases (1 January 2012 to 29 March 2023). The primary outcome was early mortality in relation to annual hospital case volume. Data were presented by volume quartiles (Qs). Restricted cubic splines were used to demonstrate the V-O relation, and the elbow method was applied to determine the optimal case volume. For clinical interpretation, numbers needed to treat (NNTs) were calculated. RESULTS: One hundred and forty studies were included, comprising 38 276 patients. A significant non-linear V-O effect was observed (P < .001), with a notable between-quartile difference in early mortality rate [10.3% (Q4) vs. 16.2% (Q1)]. The optimal annual case volume was determined at 38 cases/year [95% confidence interval (CI) 37-40 cases/year, NNT to save a life in a centre with the optimal volume vs. 10 cases/year = 21]. More pronounced between-quartile survival differences were observed for long-term survival [10-year survival (Q4) 69% vs. (Q1) 51%, P < .01, adjusted hazard ratio 0.83, 95% CI 0.75-0.91 per quartile, NNT to save a life in a high-volume (Q4) vs. low-volume centre (Q1) = 6]. CONCLUSIONS: Using this novel approach, the optimal hospital case volume threshold was statistically determined. Centralization of ATAAD care to high-volume centres may lead to improved outcomes. This method can be applied to various other cardiovascular procedures requiring centralization.

Awake extracorporeal life support and physiotherapy in adult patients: A systematic review of the literature.

OBJECTIVE: The Awake Extracorporeal Life Support (ECLS) practice combined with physiotherapy is increasing. However, available evidence for this approach is limited, with unclear indications on timing, management, and protocols. This review summarizes available literature regarding Awake ECLS and physiotherapy application rates, practices, and outcomes in adults, providing indications for future investigations. METHODS: Four databases were screened from inception to February 2021, for studies reporting adult Awake ECLS with/without physiotherapy. Primary outcome was hospital discharge survival, followed by Extracorporeal Membrane Oxygenation (ECMO) duration, extubation, Intensive Care Unit stay. RESULTS: Twenty-nine observational studies and one randomized study were selected, including 1,157 patients (males n = 611/691, 88.4%) undergoing Awake ECLS. Support type was reported in 1,089 patients: Veno-Arterial ECMO (V-A = 39.6%), Veno-Venous ECMO (V-V = 56.8%), other ECLS (3.6%). Exclusive upper body cannulation and femoral cannulation were applied in 31% versus 69% reported cases (n = 931). Extubation was successful in 63.5% (n = 522/822) patients during ECLS. Physiotherapy details were given for 676 patients: exercises confined in bed for 47.9% (n = 324) patients, mobilization until standing in 9.3% (n = 63) cases, ambulation performed in 42.7% (n = 289) patients. Femoral cannulation, extubation and V-A ECMO were mostly correlated to complications. Hospital discharge survival observed in 70.8% (n = 789/1114). CONCLUSION: Awake ECLS strategy associated with physiotherapy is performed regardless of cannulation approach. Ambulation, as main objective, is achieved in almost half the population examined. Prospective studies are needed to evaluate safety and efficacy of physiotherapy during Awake ECLS, and suitable patient selection. Guidelines are required to identify appropriate assessment/evaluation tools for Awake ECLS patients monitoring.

Preoperative P-wave parameters and risk of atrial fibrillation after cardiac surgery: a meta-analysis of 20 201 patients.

OBJECTIVES: To evaluate the role of P-wave parameters, as defined on preprocedural electrocardiography (ECG), in predicting atrial fibrillation after cardiac surgery [postoperative atrial fibrillation (POAF)]. METHODS: PubMed, Cochrane library and Embase were searched for studies reporting on P-wave parameters and risk of POAF. Meta-analysis of P-wave parameters reported by at least 5 different publications was performed. In case of receiver operator characteristics (ROC-curve) analysis in the original publications, an ROC meta-analysis was performed to summarize the sensitivity and specificity. RESULTS: Thirty-two publications, with a total of 20 201 patients, contributed to the meta-analysis. Increased P-wave duration, measured on conventional 12-lead ECG (22 studies, Cohen's d = 0.4, 95% confidence interval: 0.3-0.5, P < 0.0001) and signal-averaged ECG (12 studies, Cohen's d = 0.8, 95% confidence interval: 0.5-1.2, P < 0.0001), was a predictor of POAF independently from left atrial size. ROC meta-analysis for signal-averaged ECG P-wave duration showed an overall sensitivity of 72% (95% confidence interval: 65-78%) and specificity of 68% (95% confidence interval: 58-77%). Summary ROC curve had a moderate discriminative power with an area under the curve of 0.76. There was substantial heterogeneity in the meta-analyses for P-wave dispersion and PR-interval. CONCLUSIONS: This meta-analysis shows that increased P-wave duration, measured on conventional 12-lead ECG and signal-averaged ECG, predicted POAF in patients undergoing cardiac surgery.

Temporary mechanical circulatory support for COVID-19 patients: A systematic review of literature.

OBJECTIVE: Myocardial damage occurs in up to 25% of coronavirus disease 2019 (COVID-19) cases. While veno-venous extracorporeal life support (V-V ECLS) is used as respiratory support, mechanical circulatory support (MCS) may be required for severe cardiac dysfunction. This systematic review summarizes the available literature regarding MCS use rates, disease drivers for MCS initiation, and MCS outcomes in COVID-19 patients. METHODS: PubMed/EMBASE were searched until October 14, 2021. Articles including adults receiving ECLS for COVID-19 were included. The primary outcome was the rate of MCS use. Secondary outcomes included mortality at follow-up, ECLS conversion rate, intubation-to-cannulation time, time on ECLS, cardiac diseases, use of inotropes, and vasopressors. RESULTS: Twenty-eight observational studies (comprising both ECLS-only populations and ECLS patients as part of larger populations) included 4218 COVID-19 patients (females: 28.8%; median age: 54.3 years, 95%CI: 50.7-57.8) of whom 2774 (65.8%) required ECLS with the majority (92.7%) on V-V ECLS, 4.7% on veno-arterial ECLS and/or Impella, and 2.6% on other ECLS. Acute heart failure, cardiogenic shock, and cardiac arrest were reported in 7.8%, 9.7%, and 6.6% of patients, respectively. Vasopressors were used in 37.2%. Overall, 3.1% of patients required an ECLS change from V-V ECLS to MCS for heart failure, myocarditis, or myocardial infarction. The median ECLS duration was 15.9 days (95%CI: 13.9-16.3), with an overall survival of 54.6% and 28.1% in V-V ECLS and MCS patients. One study reported 61.1% survival with oxy-right ventricular assist device. CONCLUSION: MCS use for cardiocirculatory compromise has been reported in 7.3% of COVID-19 patients requiring ECLS, which is a lower percentage compared to the incidence of any severe cardiocirculatory complication. Based on the poor survival rates, further investigations are warranted to establish the most appropriated indications and timing for MCS in COVID-19.

Editor's Choice - Extending Aortic Replacement Beyond the Proximal Arch in Acute Type A Aortic Dissection: A Meta-Analysis of Short Term Outcomes and Long Term Actuarial Survival.

OBJECTIVE: The extent of aortic replacement during surgery for acute type A aortic dissection (ATAAD) is an important matter of debate. This meta-analysis aimed to evaluate the short and long term outcomes of a proximal aortic repair (PAR) vs. total arch replacement (TAR) in the treatment of ATAAD. DATA SOURCES: A systematic search of PubMed and Embase was performed. Studies comparing PAR to TAR for ATAAD were included. REVIEW METHODS: The primary outcomes were early death and long term actuarial survival at one, five, and 10 years. Random effects models in conjunction with relative risks (RRs) were used for meta-analyses. RESULTS: Nineteen studies were included, comprising 5 744 patients (proximal: n = 4 208; total arch: n = 1 536). PAR was associated with reduced early mortality (10.8% [95% confidence interval (CI) 8.4 - 13.7] vs. 14.0% [95% CI 10.4 - 18.7]; RR 0.73 [95% CI 0.63 - 0.85]) and reduced post-operative renal failure (10.4% [95% CI 7.2 - 14.8] vs. 11.1% [95% CI 6.7 - 17.5]; RR 0.77 [95% CI 0.66 - 0.90]), but there was no difference in stroke (8.0% [95% CI 5.9 - 10.7] vs. 7.3% [95% CI 4.6 - 11.3]; RR 0.87 [95% CI 0.69 - 1.10]). No statistically significant difference was found for survival after one year (83.2% [95% CI 77.5 - 87.7] vs. 78.6% [95% CI 69.7 - 85.5]; RR 1.05 [95% CI 0.99 - 1.11]), which persisted after five years (75.4% [95% CI 71.2 - 79.2] vs. 74.5% [95% CI 64.7 - 82.3]; RR 1.02 [95% CI 0.91 - 1.14]). After 10 years, there was a significant survival benefit for patients who underwent TAR (64.7% [95% CI 61.1 - 68.1] vs. 72.4% [95% CI 67.5 - 76.7]; RR 0.91 [95% CI 0.84 - 0.99]). CONCLUSION: PAR appears to lead to an improved early mortality rate and a reduced complication rate. In the current meta-analysis, the suggestion of an improved 10 year survival benefit of TAR was found, which should be interpreted in the context of potential confounders such as age at presentation, comorbidities, and haemodynamic stability. In any case, PAR seems to be intuitive in older patients with limited dissections, and in those presenting in less stable conditions.

Does early surgery result in improved long-term survival compared to watchful waiting in patients with asymptomatic severe aortic regurgitation with preserved ejection fraction?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In patients with asymptomatic severe aortic regurgitation with preserved ejection fraction, is early surgery superior to watchful waiting in terms of long-term survival? Altogether, 648 papers were found using the reported search, 3 of which represented the best evidence to answer the clinical question (all level III evidence). The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The 3 included studies comprised 469 patients. All 3 studies attempted to correct for potential baseline differences by different matching methods. As a result, a predominantly beneficial effect of early surgery on long-term survival in patients with severe asymptomatic AR and preserved LV function was observed, whereas none of the studies demonstrated a disadvantageous effect. Still, because many of the initially conservatively treated patients eventually proceed to surgery, longer term follow-up is warranted. Of note, older patients especially seem to adapt more poorly to chronic volume overload due to aortic regurgitation, making them potential candidates for a more aggressive approach. However, when a justified watchful waiting strategy is applied, close, extensive monitoring seems to be imperative, because the development of class I and II triggers seems to lead to improved survival.

Role of pre-operative transthoracic echocardiography in predicting post-operative atrial fibrillation after cardiac surgery: a systematic review of the literature and meta-analysis.

AIMS: This systematic review and meta-analysis aims to evaluate the role of pre-operative transthoracic echocardiography in predicting post-operative atrial fibrillation (POAF) after cardiac surgery. METHODS AND RESULTS: Electronic databases were searched for studies reporting on pre-operative echocardiographic predictors of POAF in PubMed, Cochrane library, and Embase. A meta-analysis of echocardiographic predictors of POAF that were identified by at least five different publications was performed. Forty-three publications were included in this systematic review. Echocardiographic predictors for POAF included surrogate parameters for total atrial conduction time (TACT), structural cardiac changes, and functional disturbances. Meta-analysis showed that prolonged pre-operative PA-TDI interval [5 studies, Cohen's d = 1.4, 95% confidence interval (CI) 0.9-1.9], increased left atrial volume indexed for body surface area (LAVI) (23 studies, Cohen's d = 0.8, 95% CI 0.6-1.0), and reduced peak atrial longitudinal strain (PALS) (5 studies, Cohen's d = 1.4, 95% CI 1.0-1.8), were associated with POAF incidence. Left atrial volume indexed for body surface was the most important predicting factor in patients without a history of AF. These parameters remained important predictors of POAF in heterogeneous populations with variable age and comorbidities such as coronary artery disease and valvular disease. CONCLUSION: This meta-analysis shows that increased TACT, increased LAVI, and reduced PALS are valuable parameters for predicting POAF in the early post-operative phase in a large variety of patients.