This was a single-centre, randomized controlled study comparing the difference between NT and traditional veins harvested in off-pump bypass surgery with sequential venous grafts. Two hundred patients with at least three branches of coronary artery diseases needing the left internal mammary artery and a sequential vein graft only were recruited. The enrolment of participants was determined by selecting random envelopes. The flow chart and study design schedule are presented in Figure 1.
This study recruited 200 patients with coronary heart disease who underwent off-pump coronary artery bypass grafting in cardiac surgery centre China, from December 2018 to April 2020.
The inclusion criteria were as follows: (a)aged 18–80 years; (b) at least three-vessel coronary artery disease; and (c) voluntarily joined the study and signed the informed consent form. The exclusion criteria were as follows: (a) simultaneous operations (such as heart valve or lung or abdominal surgery); (b) emergent surgery; (c) ejection fraction ≤ 35%; (d) complicated with interventricular septal perforation and ventricular aneurysm; (e) redo CABG; (f) internal diameter of great saphenous vein ≤ 0.20 cm, varicose great saphenous vein, or venous tortuosity; (g) complicated with severe malignant tumour or other serious systemic diseases; (h) severe renal insufficiency(creatinine >200 μmol/L); (i) dual antiplatelet taboo; (j) severe peripheral vascular disease; (k) allergy to the radiocontrast agent; (l) participation in other clinical trials at the same time.
Participants will be randomly assigned (at a 1:1 ratio) to the NT and CON groups with a random permuted block length of 4 patients per block to ensure that trial groups at each block are balanced. Randomization was based on the computer-generated random digits table. All random numbers were placed in a sealed opaque envelope, sealed with a stapler, and locked in the file cabinet. Patients who satisfied all inclusion criteria and did not meet any of the exclusion criteria opened the cabinet to remove the envelope and draw lots. The specific scientific research secretary kept and facilitated the random drawing of lots. The study patients were blinded.
All patients were examined using bilateral great saphenous vein ultrasonography and marked before the operation. The patients received off-pump coronary artery bypass surgery with only one sequential venous graft. If haemodynamic instability or ventricular fibrillation occurred during off-pump bypass surgery and the drug could not maintain stability, cardiopulmonary bypass was established, and surgery was performed on-pump. Then, the patient was excluded from the study. Leg wounds were sutured in three consecutive layers, and the leg wound was pressurized with an elastic bandage. The bandage was removed on the second day postoperation, and elastic socks were worn for three months. If the trunk of the vein was very slender, varicose or tortuous, it was converted using the traditional technique, and the patient was excluded from this study.
The leg incision was cut longitudinally along the ultrasound mapping line made before the operation, and the trunk of the vein was exposed. When the trunk of the vein was dissociated, approximately 2 mm of the surrounding tissue was retained on both the left and right sides. The vein was not dilated after harvesting. It was marked with a signal pen to make preparations for distinguishing the course and direction of the anastomosed vein. After removal, the vein was stored in a mixture containing heparinized saline and papaverine hydrochloride. The vein was anastomosed proximally with the ascending aorta using 6-0 polypropylene. The vein was fully predilated by aortic pressure and then examined for leakage. The sequential vein graft anastomoses were constructed end-to-side in the left and right crown systems using 7-0 or 8-0 polypropylene. The part of the vein graft with a longer distance between the two anastomoses was sutured to the heart’s surface to prevent the vein from being twisted and kinked.
The leg skin was cut longitudinally along the preoperative ultrasound marking line to expose the trunk and separate the visible branches. When the trunk of the vein dissociated, the surrounding tissue was not retained. The ankle vein was fixed using a small adaptor connected to a 10 ml syringe. The vein was dilated using a syringe filled with heparinized saline, checked for leakage, and placed in a mixture of heparinized saline and papaverine. Other operational processes were similar to those in the NT group.
All patients were given anticoagulant therapy with low molecular weight heparin after admission, and oral anticoagulants were discontinued. Patients with underlying diseases (such as hypertension, diabetes, and hyperlipidaemia) continued to take medicines until the day before the operation. Aspirin and statins were resumed 24 hours after the operation.
All patients underwent cardiac computed tomography angiography (CCTA) three months after the operation. The clinical events, recovery of the leg, and sternal wound complications were followed up.
- Primary Outcome Measure
The primary clinical end event was the occlusion rate of venous grafts three months after the operation. This was detected using cardiac computed tomography angiography (CCTA). Evaluation of graft failure: The number of failures was calculated by distal anastomosis. The graft and anastomotic failure were evaluated according to the FitzGibbon classification system . FitzGibbon-A refers to a wide range of unobstructed grafts or less than 50% narrow grafts; FitzGibbon-B is a limited flow graft with a narrowing higher than 50%. FitzGibbon-O refers to an occlusive graft without blood flow. In this study, FitzGibbon-A/B was used for patency, and FitzGibbon-O was used for graft failure. The diseased graft was also regarded as a lesion if the lesion was located at the proximal/distal anastomosis site or the graft trunk. In this study, all patients in the two groups accepted sequential grafts, which had never been before. To determine the effectiveness of the sequential grafts more early, CCTA detection was carried out in advance three months after the operation. This was different from the primary outcome measure initially planned for one year after the surgery.
- Secondary Outcome Measure
- The composite clinical events were major adverse cardiac and cerebrovascular events (MACCEs), including death from any cause, myocardial infarction, stroke, and repeat revascularization.
- The leg wound complications.
Leg complications were defined as wounds not closing after 1 month, festering wounds, or necrotic tissues present in the incision.
- Postoperative mortality
Respiratory complications, myocardial infarction, stroke, acute renal failure, and atrial fibrillation postoperatively were analysed.
- The average diameter of sequential grafts at three months
Saphenous vein expansion might have an effect on the long-term patency of sequential grafts. Therefore, we used CCTA to compare the average diameter of the sequential graft of the two groups at 3 months after the surgery. There was no such plan at the beginning of the study in the protocol. Cardiac computed tomography angiography (CCTA) was used to measure the diameter of the sequential grafts in the proximal, middle, and distal segments, and then the average diameter of the grafts was calculated. The early expansion of sequential grafts was achieved by measuring the first 100 patients’ mean diameter of sequential grafts 3 months after the operation.
Sample size calculation
Using the difference test of the comparison of the two groups of rates, α=0.05, the degree of control is 90%. The results of meta-analytic evidence indicate that the one-year patency rate of vein grafts with the traditional method is 85% and that of the no-touch method is expected to be 95%. According to the formula, the sample size of each group was 188 cases and then increased by 15% in cases of loss to follow-up, and the sample size of each group was 217 cases. Every patient had a sequential venous graft, with at least two anastomoses. According to the anastomotic ratio of 1 to 2, one anastomotic occlusion is an occurrence of the event, so the number of cases is approximately 200.
SPSS 22.0 for Mac (IBM SPSS Statistics) was used for statistical analyses. Continuous variables are reported as the mean +/− standard deviation or median (interquartile range) (IQR). Categorical variables were reported as the absolute frequency and as a percentage. Student’s t-test was applied for continuous data with equal or unequal variances. The Mann-Whitney U test was applied for continuous data that were not normally distributed. Pearson’s 2 and Fisher’s exact tests were used for categorical data. Statistical significance was accepted at p＜0.05.