Inflammatory signature-based theranostics for acute lung injury in acute type A aortic dissection.

Acute lung injury (ALI) is a serious adverse event in the management of acute type A aortic dissection (ATAAD). Using a large-scale cohort, we applied artificial intelligence-driven approach to stratify patients with different outcomes and treatment responses. A total of 2,499 patients from China 5A study database (2016-2022) from 10 cardiovascular centers were divided into 70% for derivation cohort and 30% for validation cohort, in which extreme gradient boosting algorithm was used to develop ALI risk model. Logistic regression was used to assess the risk under anti-inflammatory strategies in different risk probability. Eight top features of importance (leukocyte, platelet, hemoglobin, base excess, age, creatinine, glucose, and left ventricular end-diastolic dimension) were used to develop and validate an ALI risk model, with adequate discrimination ability regarding area under the receiver operating characteristic curve of 0.844 and 0.799 in the derivation and validation cohort, respectively. By the individualized treatment effect prediction, ulinastatin use was significantly associated with significantly lower risk of developing ALI (odds ratio [OR] 0.623 [95% CI 0.456, 0.851]; P = 0.003) in patients with a predicted ALI risk of 32.5-73.0%, rather than in pooled patients with a risk of <32.5 and >73.0% (OR 0.929 [0.682, 1.267], P = 0.642) (Pinteraction = 0.075). An artificial intelligence-driven risk stratification of ALI following ATAAD surgery were developed and validated, and subgroup analysis showed the heterogeneity of anti-inflammatory pharmacotherapy, which suggested individualized anti-inflammatory strategies in different risk probability of ALI.

Management strategies and outcomes in pregnancy-related acute aortic dissection: a multicentre cohort study in China.

BACKGROUND: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD. METHODS: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed. RESULTS: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001). CONCLUSIONS: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability. TRIAL REGISTRATION NUMBER: NCT05501145.

Inflammatory Trajectory and Anti-Inflammatory Pharmacotherapy in Frozen Elephant Trunk-Treated Acute Type I Aortic Dissection.

Background: Acute DeBakey type I aortic dissection is associated with high morbidity and mortality. Little is known regarding the role of leukocyte trajectory in prognosis. Methods: We included adult acute DeBakey type I aortic dissection patients with emergency frozen elephant trunk and total arch replacement in 2 cardiovascular centers (2020-2022). We used latent class mixed model to group patients according to their leukocyte patterns from hospital admission to the first 5 days after surgery. We investigated the association of leukocyte trajectory and 30-day and latest follow-up mortality (October 31, 2023), exploratorily analyzing the effects of ulinastatin treatment on outcome. Results: Of 255 patients included, 3 distinct leukocyte trajectories were identified: 196 in group I (decreasing trajectory), 34 in group II (stable trajectory), and 25 in group III (rising trajectory). Overall, 30-day mortality was 25 (9.8%), ranging from 8.2% (16/196) in group I, 8.8% (3/34) in group II, to 24.0% (6/25) in group III (P for trend = .036). Group III was associated with higher mortality both at 30 days (adjusted hazard ratio, 3.260; 95% CI, 1.071-9.919; P = .037) and at the last follow-up (adjusted hazard ratio, 2.840; 95% CI, 1.098-7.345; P = .031) compared with group I. Conclusions: Distinct and clinically relevant groups can be identified by analyzing leukocyte trajectories, and a rising trajectory was associated with higher short-term and midterm mortality.

Operative Mortality After Type A Aortic Dissection Surgery: Differences Based on Sex and Age.

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD). Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association. Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve. Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age (P interaction = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age (P interaction = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males. Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992).

Prognostic implication of residual inflammatory trajectories in acute type I aortic dissection: dual-center prospective cohort study.

BACKGROUND: Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined. METHODS: Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery. RESULTS: Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), ß105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126-12.574; P =0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660-0.869)], calibration, and clinical utility. CONCLUSION: Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.

Anti-inflammatory response-based risk assessment in acute type A aortic dissection: A national multicenter cohort study.

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy. Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use). Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (ß -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048). Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy.

Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) Registry protocol: rationale, design and methodology.

BACKGROUND: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS. METHOD: Thirty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [5A] registry), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. DISCUSSION: The analysis of this multicenter registry will allow our better knowledge of the prognostic importance of preoperative inflammation and different anti-inflammatory strategies in adverse events after surgery for AAS. This registry is expected to provide insights into novel different inflammatory resolutions in management of AAS beyond conventional surgical repair. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04398992 (Initial Release: 05/19/2020).

Contemporary use and outcome of Cabrol shunt in type A aortic dissection surgery: insight from China 5A study.

OBJECTIVE: Cabrol shunt has been introduced for surgical repair of type A aortic dissection (TAAD) without robust evidence supporting its routine preventive use. METHODS: Adult patients with TAAD from China 5A study were included if surgically repaired between 2016 and 2022. Primary outcome was operative mortality according to Society of Thoracic Surgeons criterion. Overall, we compared clinical outcomes in patients with and without Cabrol shunt, and subgroup analysis were further examined between Cabrol shunt and outcome among patients with or without root replacement. RESULTS: 3283 patients were finally identified for analysis, with median age of 51 (IQR 41-59) years, 2389 men, and 2201 treated with Cabrol shunt technique. Cabrol shunt-treated patients were more severely ill before surgery than those without Cabrol shunt. Overall, the rate of operative mortality was 6.6% (146/2201 in Cabrol shunt group and 71/1082 in non-Cabrol shunt group), with no association between Cabrol shunt and operative mortality (OR 1.012 (95% CI 0.754 to 1.357); p=0.938). Stratified by root replacement, Cabrol shunt was associated with similar risk of operative mortality either in patients without root replacement (OR 1.054 (0.747 to 1.487); p=0.764) or in patients with root replacement (OR 1.194 (0.563 to 2.536); p=0.644) (P interaction=0.765). Results were similar in multiple sensitivity analysis. CONCLUSION: Cabrol shunt was not associated with either a greatly lowered or an increased risk of operative mortality, regardless of aortic root replacement. Our study did not support the use of Cabrol shunt as a routine preventive strategy in the treatment of TAAD. TRIAL REGISTRATION NUMBER: NCT04398992.

Inflammatory profiles define phenotypes with clinical relevance in acute type A aortic dissection.

Association of distinct inflammatory profiles with short-term mortality is little known in type A aortic dissection (TAAD). Latent class analysis was used to identify distinct inflammatory profiles based on leukocyte, neutrophils, monocyte, lymphocytes, platelet, fibrinogen, D-dimer, neutrophils-lymphocyte ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio. We identified 193 patients with median age of 56 (IQR 47-63) years and 146 males. Patients were divided as hyper-inflammatory profiles (84 [43.5%]) and hypo-inflammatory profiles (109 [56.5%]). Although baseline characteristics were not different, hyper-inflammatory patients had higher 6-month mortality (20 [23.8%] vs. 11 [10.1%]; P = 0.014) and 30-day mortality (18 [21.4%] vs. 9 [8.3%], P = 0.009) than hypo-inflammatory patients. After adjustment for potential confounders, hyper-inflammatory profiles remain associated with higher risk of 6-month mortality than hypo-inflammatory profiles (adjusted OR 2.427 [95%CI 1.154, 5.105], P = 0.019). Assessment of preoperative inflammatory profiles adds clarity regarding the extent of inflammatory response to TAAD aetiopathologies, highlighting individual anti-inflammatory pharmacotherapy for TAAD. ClinicalTrials.gov Identifier: NCT04398992.

Prognostic Implication of Pulmonary Arterial Pressure in Surgical Repair of Predominantly Congenital Mitral Valve Regurgitation-Based Intracardiac Abnormalities.

INTRODUCTION: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities. METHODS: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012-2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP >50 mm Hg at rest or mean PAP >25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed. RESULTS: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453-2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807-3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029-1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019-1.055]), respectively. CONCLUSIONS: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP.

Proximal vs Extensive Repair in Acute Type A Aortic Dissection Surgery.

BACKGROUND: This purpose of this study was to evaluate the impact of proximal vs extensive repair on mortality and how this impact is influenced by patient characteristics. METHODS: Of 5510 patients with acute type A aortic dissection from 13 Chinese hospitals (2016-2021) categorized by proximal vs extensive repair, 4038 patients were used for for model derivation using eXtreme gradient boosting and 1472 patients for model validation. RESULTS: Operative mortality of extensive repair was higher than proximal repair (10.4% vs 2.9%; odd ratio [OR], 3.833; 95% CI, 2.810-5.229; P < .001) with a number needed to harm of 15 (95% CI, 13-19). Seven top features of importance were selected to develop an alphabet risk model (age, body mass index, platelet-to-leucocyte ratio, albumin, hemoglobin, serum creatinine, and preoperative malperfusion), with an area under the curve of 0.767 (95% CI, 0.733-0.800) and 0.727 (95% CI, 0.689-0.764) in the derivation and validation cohorts, respectively. The absolute rate differences in mortality between the 2 repair strategies increased progressively as predicted risk rose; however it did not become statistically significant until the predicted risk exceeded 4.5%. Extensive repair was associated with similar risk of mortality (OR, 2.540; 95% CI, 0.944-6.831) for patients with a risk probability < 4.5% but higher risk (OR, 2.164; 95% CI, 1.679-2.788) for patients with a risk probability > 4.5% compared with proximal repair. CONCLUSIONS: Extensive repair is associated with higher mortality than proximal repair; however it did not carry a significantly higher risk of mortality until the predicted probability exceeded a certain threshold. Choosing the right surgery should be based on individualized risk prediction and treatment effect. (ClinicalTrials.gov no. NCT04918108.).

Prognostic Impact of Systemic Coagulation-Inflammation Index in Acute Type A Aortic Dissection Surgery.

Background: A novel hematologic parameter, systemic coagulation-inflammation (SCI) index reflecting inflammation and coagulation pathways could be easily obtained from clinically routine laboratory findings. We hypothesize that the SCI index has prognostic implication in predicting operative mortality for patients with acute type A aortic dissection (ATAAD). Objectives: This study aims to investigate the prognostic value of the SCI index and to establish an SCI-adding nomogram for mortality prediction in ATAAD patients. Methods: A total of 1,967 ATAAD patients surgically repaired were collected from 12 Chinese cardiovascular centers by the 5A (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [Multicenter Retrospective Study]) study III (2016-2020). SCI index was calculated as platelet count × fibrinogen/white blood cell count on admission. By adding SCI index, a nomogram was developed and evaluated for 90-day mortality prediction with conventional predictors via the Cox model with 10-fold cross-validation. Results: Patients were stratified with low SCI (<40), middle SCI (40-100), or high SCI (>100). The 90-day survival rates increased with SCI index (low 86.9%; [95% CI: 84.9%-89.0%], middle 92.7% [95% CI: 90.9%-94.9%], and high 96.4% [95% CI: 94.2%-98.6%]; log-rank P < 0.001). SCI index is independently associated with 90-day mortality (adjusted hazard ratio: 0.549; 95% CI: 0.424-0.710; P < 0.001). The addition of SCI index provided significantly incremental prognostic value to base model including age, serum creatinine, DeBakey class, and location of intimal entry (area under the curve: 0.677; 95% CI: 0.641-0.716 vs 0.724; 95% CI: 0.685-0.760; P = 0.002), which was confirmed by net reclassification improvement index (0.158; 95% CI: 0.065-0.235; P < 0.001) and integrated discrimination improvement index (0.070; 95% CI: 0.007-0.036; P < 0.001). Conclusions: SCI index is easily obtainable, performs moderately well as a predictor of short-term mortality in ATAAD patients, and may be useful for risk stratification in emergency settings. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [Multicenter Retrospective Study] III NCT04918108).

A Novel Inflammation-Based Risk Score Predicts Mortality in Acute Type A Aortic Dissection Surgery: The Additive Anti-inflammatory Action for Aortopathy and Arteriopathy Score.

Objective: To develop an inflammation-based risk stratification tool for operative mortality in patients with acute type A aortic dissection. Methods: Between January 1, 2016 and December 31, 2021, 3124 patients from Beijing Anzhen Hospital were included for derivation, 571 patients from the same hospital were included for internal validation, and 1319 patients from other 12 hospitals were included for external validation. The primary outcome was operative mortality according to the Society of Thoracic Surgeons criteria. Least absolute shrinkage and selection operator regression were used to identify clinical risk factors. A model was developed using different machine learning algorithms. The performance of the model was determined using the area under the receiver operating characteristic curve (AUC) for discrimination, calibration curves, and Brier score for calibration. The final model (5A score) was tested with respect to the existing clinical scores. Results: Extreme gradient boosting was selected for model training (5A score) using 12 variables for prediction-the ratio of platelet to leukocyte count, creatinine level, age, hemoglobin level, prior cardiac surgery, extent of dissection extension, cerebral perfusion, aortic regurgitation, sex, pericardial effusion, shock, and coronary perfusion-which yields the highest AUC (0.873 [95% confidence interval (CI) 0.845-0.901]). The AUC of 5A score was 0.875 (95% CI 0.814-0.936), 0.845 (95% CI 0.811-0.878), and 0.852 (95% CI 0.821-0.883) in the internal, external, and total cohort, respectively, which outperformed the best existing risk score (German Registry for Acute Type A Aortic Dissection score AUC 0.709 [95% CI 0.669-0.749]). Conclusion: The 5A score is a novel, internally and externally validated inflammation-based tool for risk stratification of patients before surgical repair, potentially advancing individualized treatment. Trial Registration: clinicaltrials.gov Identifier: NCT04918108.

Laboratory signatures differentiate the tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery.

OBJECTIVES: Our goal was to investigate whether laboratory signatures on admission could be used to identify risk stratification and different tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery. METHODS: Patients from 10 Chinese hospitals participating in the Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) study were randomly divided into derivation and validation cohorts at a ratio of 7:3 to develop and validate a simple risk score model using preoperative variables associated with in-hospital mortality using multivariable logistic regression. The performance of the model was assessed using the area under the receiver operating characteristic curve. Subgroup analyses were performed to investigate whether the laboratory signature-based risk stratification could differentiate the tolerance to hypothermic circulatory arrest. RESULTS: There were 1443 patients and 954 patients in the derivation and validation cohorts, respectively. Multivariable analysis showed the associations of older age, larger body mass index, lower platelet-neutrophile ratio, higher lymphocyte-monocyte ratio, higher D-dimer, lower fibrinogen and lower estimated glomerular filtration rate with in-hospital death, incorporated to develop a simple risk model (5A laboratory risk score), with an area under the receiver operating characteristic of 0.736 (95% confidence interval 0.700-0.771) and 0.715 (95% CI 0.681-0.750) in the derivation and validation cohorts, respectively. Patients at low risk were more tolerant to hypothermic circulatory arrest than those at middle to high risk in terms of in-hospital mortality [odds ratio 1.814 (0.222-14.846); odds ratio 1.824 (1.137-2.926) (P = 0.996)]. CONCLUSIONS: The 5A laboratory-based risk score model reflecting inflammatory, immune, coagulation and metabolic pathways provided adequate discrimination performances in in-hospital mortality prediction, which contributed to differentiating the tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery.Clinical Trials. gov number NCT04918108.

Anti-Inflammatory Effect of Ulinastatin on the Association Between Inflammatory Phenotypes in Acute Type A Aortic Dissection.

Background: Acute type A aortic dissection (ATAAD) is a heterogeneous systemic inflammatory response syndrome. Identification of distinct inflammatory phenotypes may allow more precise therapy and improved care. We aim to investigate whether distinct inflammatory subphenotypes exist in ATAAD patients and respond differently to pharmacotherapies. Methods: Retrospective analysis of data sets was conducted from the Additive Anti-inflammatory Actions for Aortopathy & Arteriopathy (5A) III study. Inflammatory subphenotypes were derived among 2008 ATAAD patients who received surgical repair at 11 Chinese hospitals (2016-2020) using latent class analysis applied to 14 laboratory signatures within 6 hours of hospital admission. Outcomes included operative mortality (Society of Thoracic Surgeons definition), derived subphenotype frequency, and the potential consequences of phenotype frequency distributions on the treatment effects. Results: The median (interquartile range) age of patients was 54 (45-62) years, and 1423 (70.9%) were male. A two-class (two subphenotype) model was an improvement over a one-class model (P<·001), with 1451 (72.3%) patients in the hypoinflammatory subphenotype group and 557 (27.7%) in the hyperinflammatory subphenotype group. Patients with the hyperinflammatory subphenotype had higher operative mortality (71 [12.7%] vs 127 [8.8%]; P=0·007) than did those with the hypoinflammatory subphenotype. Furthermore, the interaction between ulinastatin treatment and subphenotype is not significant for operative mortality (P=0.15) but for ventilator time (P=0·04). Conclusion: Two subphenotypes of ATAAD were identified in the 5A cohort that correlated with clinical outcomes, with significant interaction effect between anti-inflammatory treatment and subphenotypes for ventilator time, suggesting these phenotypes may help in understanding heterogeneity of treatment effects. Trial Registration: Clinical Trials. Gov: number NCT04918108.

Circulating biomarker-based risk stratifications individualize arch repair strategy of acute Type A aortic dissection via the XGBoosting algorithm.

Aims: The incremental usefulness of circulating biomarkers from different pathological pathways for predicting mortality has not been evaluated in acute Type A aortic dissection (ATAAD) patients. We aim to develop a risk prediction model and investigate the impact of arch repair strategy on mortality based on distinct risk stratifications. Methods and results: A total of 3771 ATAAD patients who underwent aortic surgery retrospectively included were randomly divided into training and testing cohorts at a ratio of 7:3 for the development and validation of the risk model based on multiple circulating biomarkers and conventional clinical factors. Extreme gradient boosting was used to generate the risk models. Subgroup analyses were performed by risk stratifications (low vs. middle-high risk) and arch repair strategies (proximal vs. extensive arch repair). Addition of multiple biomarkers to a model with conventional factors fitted an ABC risk model consisting of platelet-leucocyte ratio, mean arterial pressure, albumin, age, creatinine, creatine kinase-MB, haemoglobin, lactate, left ventricular end-diastolic dimension, urea nitrogen, and aspartate aminotransferase, with adequate discrimination ability {area under the receiver operating characteristic curve (AUROC): 0.930 [95% confidence interval (CI) 0.906-0.954] and 0.954, 95% CI (0.930-0.977) in the derivation and validation cohort, respectively}. Compared with proximal arch repair, the extensive repair was associated with similar mortality risk among patients at low risk [odds ratio (OR) 1.838, 95% CI (0.559-6.038); P = 0.316], but associated with higher mortality risk among patients at middle-high risk [OR 2.007, 95% CI (1.460-2.757); P < 0.0001]. Conclusion: In ATAAD patients, the simultaneous addition of circulating biomarkers of inflammatory, cardiac, hepatic, renal, and metabolic abnormalities substantially improved risk stratification and individualized arch repair strategy.

Incidence and Outcome of Acute Myocardial Infarction in Patients With Aortic Dissection and Risk Factor Control.

Background and Aims: The contradiction of management modality between acute myocardial infarction(AMI) and aortic dissection(AD) may result in clinical catastrophe. Data on risk factors, incidence, and outcome of AD and AMI are limited, and there have been no studies on the long-term outcomes of AMI in patients with AD. So we aimed to investigate long-term outcomes after AMI in patients with AD, and propose a useful diagnostic paradigm. Methods: Consecutively enrolled patients with AD and AMI who were referred to our center from 2010 to 2017. Baseline patient characteristics, risk factors, all medical treatments, echocardiographic parameters, laboratory data, and treatment were recorded. All patients were followed up from the first hospitalization until a first heart event, death, or 17 March, 2018. Results: 0.13% in AMI and 7.49% in AD patients had a concomitant diagnosis of AD and AMI. The average patient age was 53.3 ± 12.1 years and 84.6% were male. The most prevalent vascular risk factors were hypertension (69.2%) and current smoker (64.1%). Of all the 39 patients, 66.7% were managed surgically. Overall in-hospital mortality was 10.3%. The 30-day and 5-year fatality rates were 23.1% and 35.9%, but were higher for female than for male (66.7 vs. 30.3%, log-rank P = 0.045) on 5-year mortality. The overall survival of females was inferior to the males (log-rank P = 0.045). Conclusions: Patients with AMI and AD exhibit high 5-year fatality rates. For these patients, surgical management tends to have lower mortality. Improved management of hypertension and smoking, may reduce future incidence rates.

The use of cIMT as a predictor of postoperative stroke in patients undergoing surgical repair of acute type a aortic dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires surgical intervention. Stroke remains an extremely serious adverse outcome that can occur in ATAAD patients undergoing aortic arch repair, leading to higher rates of patient mortality and decreased postoperative quality of life. In the present study, we sought to determine whether carotid intima-media thickness (cIMT) is a reliable predictor of postoperative stroke risk. MATERIALS AND METHODS: This was a prospective study of 76 patients with ATAAD undergoing aortic arch repair. For all patients, cIMT was determined preoperatively through a Doppler-based method. Incidence of different forms of neurological dysfunction, including temporary neurological dysfunction (TND) and stroke, was monitored in these patients, and the relationship between cIMT and stroke incidence was assessed using a receiver-operating characteristic (ROC) curve. Prognostic variables associated with stroke risk were further identified through univariate and multivariate analyses. RESULTS: A total of 26/76 (34.2%) patients in the present study suffered from neurological dysfunction, of whom 16 (21.0%) suffered from TND and 10 (13.2%) suffered a stroke. The remaining 50 patients (65.8%) did not suffer from neurological dysfunction. The cIMT values in the stroke, TND, and neurological dysfunction-free patients in this study were 1.12 ± 0.19 (mm), 0.99 ± 0.13 (mm), and 0.87 ± 0.13 (mm), respectively. A total of 4 patients in this cohort died during the study, including 1 in the TND group and 3 in the stroke group. An ROC curve analysis indicated that cIMT could predict stroke with an area under the curve value of 0.844 (95% CI, 0.719-0.969; p < 0.001). A multivariate analysis revealed that cIMT > 0.9 mm was independently associated with stroke risk (p = 0.018). CONCLUSION: We found that cIMT can be used to predict postoperative stroke risk in ATAAD patients undergoing aortic arch repair, with a cIMT > 0.9 mm coinciding with increased stroke risk in these patients. TRIAL REGISTRATION: ChiCTR1900022289. Date of registration 4 April 2019 retrospectively registered.

Haematocrit differences modify the association of cardiopulmonary bypass reoxygenation with acute kidney injury after paediatric Tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the potential impact of haematocrit differences in the association between cardiopulmonary bypass reoxygenation and acute kidney injury following Tetralogy of Fallot repair. METHODS: We investigated the association of perfusate oxygenation during aortic occlusion associated with acute kidney injury between 204 normal and 248 higher haematocrit children with Tetralogy of Fallot, aged 1 month-18 years, who were surgically repaired in 2012-2018. Normal and higher haematocrit children were defined as having a preoperative haematocrit within and above age- and sex-specific reference intervals, respectively. Acute kidney injury was determined as a binary variable according to the Kidney Disease Improving Global Outcomes criteria. RESULTS: After adjusting for baseline and clinical covariates, a significant interaction between the haematocrit and continuous perfusate oxygenation on acute kidney injury was found (pinteraction = 0.049): a higher perfusate oxygenation was associated with a greater acute kidney injury risk among higher haematocrit children (adjusted odds ratio = 1.50, 95% confidence interval = [1.02, 2.22] per SD, p = 0.038) but not among normal haematocrit children (adjusted odds ratio = 0.91, 95% confidence interval = [0.51, 1.63] per SD, p = 0.73). After a similar adjustment, there was a marginal interaction between tertiles of perfusate oxygenation and haematocrit on acute kidney injury (pinteraction = 0.09): the middle and top tertiles of perfusate oxygenation were associated with a trend towards increased acute kidney injury risks among higher haematocrit children (adjusted odds ratio = 1.69, 95% confidence interval = [0.61, 4.66]; adjusted odds ratio = 2.25, 95% confidence interval = [0.84, 5.99], respectively) but not among normal haematocrit children (adjusted odds ratio = 1.16, 95% confidence interval = [0.46, 2.94]; adjusted odds ratio = 0.45, 95% confidence interval = [0.15, 1.36], respectively) compared with the bottom tertile. CONCLUSION: Preoperative haematocrit differences significantly modify the association of perfusate oxygenation with acute kidney injury, highlighting differential control of reoxygenation for different haematocrit children with Tetralogy of Fallot in the management of cardiopulmonary bypass.

Renal malperfusion affects operative mortality rather than late death following acute type A aortic dissection repair.

OBJECTIVE: The aim of our study was to assess how much renal malperfusion increases the risk of early and late mortality in patients with acute type A aortic dissection (ATAAD) undergoing surgical repair. METHODS: This study included 218 patients with ATAAD undergoing surgical repair using the total arch replacement and frozen elephant trunk technique. Mean age was 47.8 ± 10.7 years and 170 were male (78.0%). Based on clinical symptoms and computed tomographic angiography (CTA) findings, 48 patients were diagnosed with preoperative renal malperfusion (22.0%). Clinical data were compared between two groups. The impact of renal malperfusion on operative and late mortality were evaluated with Cox regression. RESULTS: Patients with renal malperfusion experienced significantly higher incidences of persistent postoperative acute kidney injury (AKI; 10/48, 20.8% vs 7/170, 4.1%; p < 0.001) and transient AKI (10/48, 20.8% vs 8/170, 4.7%; p = 0.001) as well as operative mortality (22.9%, 11/48 vs 8.3%, 14/170; p = 0.023). Five-year survival was significantly lower in the renal malperfusion group (72.9% vs 87.0%, p = 0.003). Renal malperfusion was the risk factor for operative mortality (hazard ratio, HR, 2.74; 95% CI, 1.07-6.99; p = 0.035) and overall mortality (HR, 2.64; 95% CI, 1.23-5.67; p = 0.013) but did not predict late death (HR, 2.46; 95% CI, 0.65-9.35; p = 0.187). CONCLUSION: Renal malperfusion increases the risk of operative mortality by 3 times but did not affect late death in patients undergoing acute type A dissection repair.