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


INTRODUCTION
2][3][4] Cabrol shunt or Cabrol fistula, also known as a 'perigraft-to-right atrial shunt', is a technique used for uncontrolled bleeding during graft replacement of ascending aortic and aortic root within the aneurysmal sac (inclusion technique). 46][7] Therefore, Cabrol shunt has been proposed as an effective technique to control bleeding in surgical repair of TAAD, especially in cases of excessive or uncontrolled bleeding, coagulation disorder and reoperation.In addition to the classic Cabrol shunt, several modified Cabrol shunt

WHAT IS ALREADY KNOWN ON THIS TOPIC
⇒ Cabrol shunt is a technique used for uncontrolled bleeding during graft replacement of ascending aortic and aortic root within the aneurysmal sac.⇒ Cabrol shunt has been used as a technique to control bleeding in surgical repair of type A aortic dissection, especially in cases of excessive or uncontrolled bleeding, coagulation disorder and reoperation.

WHAT THIS STUDY ADDS
⇒ Cabrol shunt was not associated with either a greatly lowered or an increased risk of operative mortality.⇒ Cabrol shunt was associated with similar risk of operative mortality either in patients without root replacement or in patients with root replacement, without interaction effect.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
⇒ Cabrol shunt as a routine preventive strategy should be used with caution in the treatment of type A aortic dissection.
techniques subsequently were described and applied in either open or inclusion repair of aortic dissection for the prophylactic, routine or remedial purpose, with satisfactory haemostasis results. 8 9However, Cabrol shunt usually requires preserving its naïve aortic wall, which limited precise anatomic reconstruction as well as heart failure and severe pulmonary hypertension if the shunt did not close in the short-term. 10 11urrently, Cabrol shunt and its modifications remains used in part of Chinese aortic centres when dealing with surgical repair of TAAD.However, surgical management of aortic aneurysms/dissections has changed in the last decades, so a detailed knowledge is mandatory for adequate interpretation of current use and outcomes of Cabrol shunt techniques.In this multicentre observational study from China, we investigate the perioperative outcomes of Cabrol shunt and to determine whether Cabrol Shunt can be a routinely preventive procedure in TAAD surgery.

Study design and ethical approval
The China Additive Anti-inflammatory Action for Aortopathy and Arteriopathy (5A) registry study is an ongoing prospective, multicentre cohort registry designed to collect data on clinical backgrounds and outcomes of patients hospitalised for aortic dissection since January 2016.This present study was conducted in accord with the Declaration of Helsinki and registered in ClinicalTrials.
gov.Patient written consent for the publication of the study data was waived due to this retrospectively observational study.Patient selection, data collection and data analysis were performed in accordance with STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines and TRIPOD guidelines (Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis). 12 13

Patient selection
From January 2016 to December 2022, consecutive patients with acute type A aortic dissection (ATAAD) hospitalised through the emergency department at participating hospitals were retrospectively identified from six hospitals of China 5A study at their first admission and then followed after discharge (figure 1).ATAAD was defined as any dissection involving the ascending aorta on contrast-enhanced CT, within 14 days of symptom onset.Preoperative diagnosis was made on contrast-enhanced CT angiography.Patients 18 years of age or older were included if they underwent aortic surgery within 14 days from symptom onset to hospital arrival.Key criteria for exclusion included type B aortic dissection, recurrent aortic dissection, traumatic aortic dissection and iatrogenic aortic dissection.

Data collection
Patient information obtained included demographic data, medical history and risk factors, baseline characteristics, surgical procedures, pharmacotherapeutics, critical  Aortic and vascular disease care and discharge.The detailed definitions and measures of cigarette smoking, alcohol consumption, body mass index, hypertension, diabetes mellitus, arrhythmia and malperfusion was previous in our recent report. 14ll central laboratories at participating sites have been recognised and certified by the China National Accreditation Service for Conformity Assessment of Laboratory.

Surgical procedure
Surgical treatment of TAAD were mainly approached by two basic methods: placement of an interposition graft

Laboratory profiles
Leucocyte (×10 9 /L) 8.1 (6.0 to 11.9) 8.9 (6.5 to 12.  with resection of the dissected tissue, and the inclusion graft technique in which the remnant of the native aorta is wrapped around the graft.Graft inclusion was performed according to the technique described by Bentall. 15The ascending aorta was reserved and was incised longitudinally, and Dacron graft was anastomosed inside and into the true lumen of the aorta.The remnant of the native aorta is wrapped around the graft, and a surgical fistula (Cabrol shunt) from the periaortic space to the right atrium was created to decompress the perigraft space for control of bleeding (autotransfusion).Several modifications of Cabrol shunt have been performed in surgical repair of TAAD, in which a perigraft compartment is created by the placement of an autologous pericardium or a bovine pericardial patch that is wrapped around the graft.The decision to perform Cabrol shunt was in a nonrandomised fashion and at the surgeon's discretion for the purpose of prophylactic, routine or remedial use.

Outcome
The primary outcome was operative mortality, defined as any death, regardless of cause, occurring within 30 days after surgery in or out of the hospital and after 30 days during the same hospitalisation subsequent to the operation according to the Society of Thoracic Surgeons criteria. 16Other outcomes were 30-day mortality, mechanical ventilation time and intensive care unit stay.
Malperfusion was defined as end-organ ischaemia caused by branch vessel involvement and resulting in functional impairment. 17In this study, the follow-up for patients was concluded 30 days after surgery, hospital discharge or the death occurring during the same hospitalisation subsequent to the operation, which ever last.

Statistical analysis
Logistic regression was used to estimate the association between Cabrol shunt and outcome by OR and 95% CI.This association was further evaluated with adjustment for the potential baseline, demographic, comorbidity, clinical and laboratory confounders.9][20] In particular, GenMatch is a matching technique that combines PS matching with multivariate matching, which weights the PS and the observed individual variables based on an automated search algorithm and iteratively checks the balance and directs the search to ward the best matches (those that optimise balance). 21e performed subgroup analysis to investigate whether there was an interaction between Cabrol shunt, aortic root replacement and operative mortality. 22e further calculated the number needed to treat, which is a measure that indicates how many patients on average need to be treated with Cabrol shunt to prevent an average of one patient from operative death, or the number needed to harm, which is a measure that indicates how many patients on average need to be exposed to Cabrol shunt to cause death in an average of one patient who would not otherwise die. 23ontinuous data were presented as mean (SD) or median (IQRs) compared by t-test or Mann-Whitney test, and categorical data were reported as percentages (%) compared by χ 2 test or Fisher exact test.P values were two-tailed, with p value<0.05 considered statistically significant unless otherwise stated.Statistical analysis was performed using R software, Stata statistical software and Python programming software.

Patient characteristics and outcome
Three thousand two hundred and eighty-three patients were finally identified for analysis, with median age of 51 (IQR 41-59) years and 2389 men, of whom 2201 underwent Cabrol shunt technique.Patient characteristics and perioperative outcomes stratified by absence versus presence of Cabrol shunt technique were presented in table 1. 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 the Cabrol shunt group and 71/1082 in the non-Cabrol shunt group).

Subgroup analysis of root procedure
The rate of aortic root replacement was 14.2% (154/1082) in the non-Cabrol shunt group and 50.3% (1107/2201) in the Cabrol shunt group (p<0.001).Stratified by root procedure, patients with Cabrol shunt were likely to have similar risk of operative mortality compared with those without in patients without root replacement (OR 1.054 (0.747 to 1.487); p=0.764) and in patients with root replacement (OR 1.194 (0.563 to 2.536); p=0.644) (P interaction=0.765).After additional adjustment for multivariable and PS analysis, the results were still similar (figure 2; online supplemental table S1).

Number needed to treat or harm analysis
Overall, the number needed to harm was 1428 patients (95% CI −55 to 56; no significant) receiving Cabrol shunt for one patient to cause operative death compared without receipt of Cabrol shunt.Figure 3 showed the number needed to treat or harm analysis across the subgroup within root procedure (with or without root replacement).

DISCUSSION
In this large sample of TAAD population from China 5A study, we investigated the contemporary use and outcome of Cabrol shunt in TAAD.Overall, no significances were observed between non-Cabrol and Cabrol Bleeding complications with aortic root replacement have prompted development of techniques by which the graft is wrapped with the remaining native aorta to control bleeding.Cabrol and colleagues extended this idea by creating a fistula between the periprosthetic space and the right atrium to prevent development of a haematoma under tension with eventual tearing of the aortic wall. 4 7abrol shunt and its modifications has evolved over the years as an important contribution to controlling haemorrhage in surgical repair of aortic dissection.Much of the early enthusiasm for Cabrol shunt focused on an expected advantage in patients with complex root reconstructions, secondary thoracotomy, coagulation disorders or long-term treatment of aspirin or a preoperative thrombolysis for a presumed myocardial infarction. 24In the last decades several technical, materials and pharmacological improvements allowed application of the open technique in TAAD, including zero porosity grafts, tissue glue and polytetrafluoroethylene felts. 25 26Given more surgeons abandoned the inclusion technique in favour of the open technique of dissection repair, the application of Cabrol shunt is increasingly rare in surgical repair of TAAD.
Inconsistent with some previous studies, 5-9 our findings showed the associations observed between Cabrol shunt and operative mortality were not significant across different population subgroups (ie, absence or presence of aortic root replacement), although risk varies to differing extents.Our results suggested that patients with Cabrol shunt did not benefit or harm more than those without Cabrol shunt, regardless of root replacement.These results were similar in multiple sensitivity analysis.
It might be explained by the fact that those patients who underwent Cabrol shunt in previous studies were at high risk of excessive bleeding, uncontrollable bleeding, coagulation disorders, complex root procedures or reoperation and Cabrol shunt were applied mainly for the purpose of prophylactic preference. 9 24 27 28n the contrary, these patients induced in our study are non-selected, regardless of risk stratifications and Cabrol shunt were applied for different purposes, including prophylactic, routine or remedial preference.In addition, previous studies began several years before our study, during a time when open-repair devices, techniques and strategies were changing rapidly.The quality of the surgical procedure may affect perioperative clinical outcomes, especially for this emergency surgical repair of TAAD.It is less clear that higher surgical quality would result in better operative outcomes after open repair, but it is possible that the steep learning curve for open repair resulted in differences in surgical quality that were reflected in later results.As a result, it makes this procedure seemingly less desirable for use in aortic surgery, especially in root replacement.
Our study has important clinical implications.Although our study showed no statistical difference between the non-Cabrol and Cabrol groups, it does not mean that the Cabrol procedure lost clinical application value in aortic surgery, mainly due to the lack of further subgroup analysis in terms of use purpose to the great extent.A recent study from Elefteriades and colleagues investigated its effectiveness in controlling bleeding, persistent left-toright shunt, anastomotic pseudoaneurysm and operative, hospital and long-term survival. 29In their study, recalcitrant bleeding was successfully controlled by the Cabrol fistula in all 17 patients, and only 2 patients required re-exploration for clot evacuation.These patients all survived to discharge, except for three cases consisting of two deaths from multiple organ failure and one death Aortic and vascular disease from intraoperative technical difficulties.In no case did echocardiography (ECHO) identify sustained left-to-right shunting or any patent shunt beyond a few days postoperatively and later CT scan identify continued flow via the Cabrol shunt or any evidence of anastomotic pseudoaneurysm, showing extremely favourable experience for control of intractable intraoperative bleeding in aortic surgery.Similarly positive outcomes have been found in other centres as well. 24 30Therefore, it emphasises the importance and necessity of determining the exact indications for previous Cabrol shunt use, especially in case of intractable intraoperative bleeding in some complex, extensive or emergent procedures compared with the conventional method of packing an open chest.

Limitation
Our study is not devoid of limitations.First of all, due to the lack of sufficient and precise information about the purpose of this method for each patient in which Cabrol shunt was primarily used for the one of the following purposes: prophylactic, routine or remedial, our findings could still be affected by a residual treatment selection bias despite multivariate adjustment and PS analysis.Second, our database does not provide complete information regarding the incidence rate of pseudoaneurysm formation, which might have an important effect on the interpretation of these current results.Finally, the 5A does not contain information on long-term survival outcomes and quality of life.Adverse outcomes might lead to a decreased quality of life and thus, mitigate the beneficial effect on operative mortality resulting in fewer quality-adjusted life years.

CONCLUSION
Relying on this large sample study, we found that Cabrol shunt was not associated with either a greatly lowered or an increased risk of operative mortality.This is consistently constant in each subgroup with regard to root replacement.These results suggested that patients did not benefit more from Cabrol shunt with regards to operative mortality.Our study did not support the use of the Cabrol shunt as a routine preventive strategy in the treatment of TAAD.
Contributors HLiu contributed to the collection, assembly and quality control of the data.HLiu was responsible for the conception and design of the study.HLi revised papers and supplement key data.HLiu, MS, SQ and BS designed the strategies of data analysis and conducted the statistical analysis.All authors interpreted the data.HLiu, MS and HLi drafted the report.All authors revised it critically for important intellectual content and agreed to submit the report for publication.HLiu accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

Figure 3
Figure 3 Number needed to treat or harm analysis.(A) Overall population; (B) subgroup by root replacement.NNH, number needed to harm; NNT, number needed to treat; CI=CI interval.

Table 1
Patient characteristics, operative data and outcomes

Table 2
Associations between Cabrol shunt and operative mortality in the crude analysis, multivariable analysis and propensity score analyses profiles.‡Adjustmentfor age, sex, body mass index, cardiovascular risk factors and laboratory profiles, as well as coagulation-related parameters.
*Adjustment for coagulation-related parameters (platelet, D-dimer, haemoglobin, international normalised ratio and activated partial thromboplastin time).†Adjustment for age, sex, body mass index, cardiovascular risk factors and laboratory

Favor use Cabrol shunt Favor no use Cabrol shunt
Figure 2 Subgroup analysis of association between Cabrol shunt and primary outcome.(A)Subgroup analysis by root replacement.*Adjustmentfor age, sex, body mass index, cardiovascular risk factors and laboratory profiles, as well as coagulation-related parameters (platelet, D-dimer, haemoglobin, international normalised ratio and activated partial thromboplastin time).IPTW, inverse probability of treatment weighting; PS, propensity score.Liu H, et al.Open Heart 2023;10:e002465.doi:10.1136/openhrt-2023-002465shuntregarding operative mortality.By subgroup analysis, Cabrol shunt was likely to have similar risk of operative mortality to non-Cabrol shunt regardless of aortic root replacement.Results were similar in multiple sensitivity analysis.