Long-term clinical outcomes after coronary artery bypass grafting with pedicled saphenous vein grafts

Coronary artery bypass grafting (CABG) is the recommended treatment for coronary artery disease (CAD) involving complex lesions in multiple vessels, with a survival benefit compared to percutaneous coronary intervention (PCI) [1–4]. Saphenous vein grafts (SVG) are most often used but are subject to graft disease [5] and their reduced long-term patency compared to left internal mammary artery (IMA) grafts is well established [6, 7]. The success of CABG depends arguably on the long-term patency rate of the conduits and several risk factors for graft failure have been identified [8–10]. Although most risk factors are related to the target vessel and cannot be influenced, damage to graft vessels during surgical preparation and dilation has also been shown to influence patency [11]. More than 20 years ago Souza et al. initiated studies of vein grafts harvested with a pedicle of surrounding tissue and without distending the grafts [12]. This “no-touch” (NT) technique is believed to preserve the vein vasa vasora [13] and the grafts exhibit a slower progression of intimal hyperplasia [14] and atherosclerosis [15]. A single-center randomized clinical trial with angiographic follow-up of these grafts from has demonstrated significantly higher patency for NT harvested veins compared with veins harvested with the conventional technique [16] as well as with radial artery grafts [17]. The patency of NT grafts was comparable to that of the IMA still 16 years after surgery [18]. The influence on clinical outcome, that the presumably improved patency of grafts harvested with the NT technique could entail, has however not been studied.

The Swedish personal identity number allows nationwide registries with the possibility of long-term follow-up. The Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry [19, 20] provides data on all patients undergoing cardiac surgery in Sweden as well as records of angiographies and coronary interventions. Mortality yields limited information when used as sole outcome in studies of graft patency, as it is most probably only to a lesser degree influenced by the effects of failing grafts after CABG surgery [8]. In the present study we use incidence of clinically-driven angiography and need for repeat intervention as endpoints, in addition to mortality, for evaluation of long-term results after CABG. These outcomes are likely to have a high association with symptomatic graft failure and related events and have been used previously to evaluate results after CABG [21]. Cardiac surgeons in Örebro have implemented the NT practice in a majority of cases since more than 10 years whereas vein grafts are harvested with a conventional technique in other centres in Sweden. Data on vein harvesting technique for patients operated in Örebro is available in a local registry. Here, we evaluate outcomes in the more than 1300 patients operated with CABG using NT vein grafts during the last 10 years in an observational propensity matched cohort study. We aim to quantify the mortality, incidence of first angiography and need for repeat intervention and evaluate possible differences in between patients operated in Örebro with the NT technique and Swedish patients operated with the conventional technique.

In this study NT grafting was associated with a lower risk for repeat angiography, however no difference could be observed for mortality and need for reintervention. Earlier reported improvements in patency of NT veins are possibly reflected in an improved clinical outcome during the first 10 years after surgery.

Although the NT technique has been used in practice for more than 15 years, the evidence for this method is limited to studies with a small number of patients that have demonstrated improved angiographic patency. It has been unknown how this apparent improved patency translates into an improved clinical outcome. Main determinants of vein graft failure has been proposed to be a small vessel diameter, reduced wall motion of the vessel-dependent myocardial region and the right coronary as target vessel [10]. This indicates that it often are grafts supplying less important myocardial regions that fail and perhaps why they generally do so without any symptoms and seemingly without increasing the mortality or risk of myocardial infarction [8]. An improvement in overall patency does therefore not necessarily confer a better clinical result and may explain the lack of improvements in outcome with multiple arterial grafts [21, 22]. In the first randomised angiographic study of the NT vein, the patency in the group with conventional harvesting technique was high and the difference in patency between groups was initially small [12]. This difference later increased gradually but was not significant and clinically relevant until the 8.5 and 16 years follow-up [16, 18]. The mean follow-up in this study may therefore be too short to detect differences in clinical events.

There are large regional variations in Sweden how many CABG procedures are performed per number of inhabitants (Fig. 2). Although partly explained by demographics and differences in incidence of coronary artery disease (CAD) in the population, a substantial part of the variation is the result of a difference in the indications and threshold for referral for surgery versus PCI. According to the 2015 annual report from the SWEDEHEART registry, the number of patients referred for CABG surgery in Örebro ranged between 25.4 and 28.2 per 100,000 inhabitants, which is close to the national average of 26.3. The incidence of angiography may reflect the return of CAD symptoms but is highly influenced by other factors such as rates of surveillance with functional studies and the physician threshold for repeat angiography versus optimization of medical therapy. Surgeons in the Örebro region could be performing technically better and medical therapy given to patients after surgery that could influence long-term results [23] is possibly subjected to regional differences. There is thus a possibility for regional variability during follow-up that could introduce confounding. The vast majority of patients in Örebro were operated with the NT technique making the patients receiving conventional vein grafts in this institution a highly selected population depending on several factors not included in the baseline data. Conventional vein harvesting is more often preferred in more fragile patients where quick and simple surgery is the priority, especially in women in whom the harvesting of NT veins might be technically more demanding. NT is favored in patients with expected long survival, but also in patients with coronary vessels of poor quality. In order to avoid confounding patients with conventional vein grafts operated in Örebro were therefore not included in the analysis. Neither the configuration of the grafts nor the targeted vessels or their degree of obstruction can be identified in the registry. There was no formal definition of an occluded or significantly stenosed graft and it was completely operator-dependent. Data on graft failure was not available on an individual graft level and there was no information from the angiography procedure regarding number of failed grafts, their targets or the graft type. It is impossible to establish when a graft failed, what type it was or if the presence of the failed graft in any way was a contributing cause of the symptoms preceding the angiography.

In the present registry-study we use incidence of first clinically-driven angiography and need for repeat intervention as endpoints for evaluation long-term results as they are believed to have a high correlation with symptoms of CAD including symptomatic graft failure. An improvement in the risk for new angiography could be seen for the NT group but not for the need of repeat intervention or survival. The distribution of different indications for the angiography was similar between the groups supporting the view that the incidences of angiography and reintervention in the two groups are similarly linked to an incidence of new coronary events and return of CAD symptoms. Failed grafts were less commonly found during angiography of NT patients as compared to patients with conventional grafts. A smaller proportion of patients in the NT group seem to return with CAD symptoms relating to pathology in the grafts or with concurrent asymptomatic graft failures further supporting the findings in this study and in earlier angiographic studies of NT veins. The study design does, however, not exclude the possibility of residual confounding and a randomized multicentre study needed to confirm these results is being planned.

In the current study we present follow-up data after CABG from a large Swedish data registry covering all 8 centres. We evaluated results of CABG patients operated in Örebro using the NT technique for vein harvest, comparing outcome with a propensity score matched cohort of patients operated with a conventional harvesting technique in other centres in Sweden. An improvement in the risk for new angiography for the NT group compared to the group with conventional vein harvesting could be observed, however no difference could be observed for mortality and need for reintervention. Earlier reported improvements in patency of NT veins are thereby possibly reflected in an improved clinical outcome during the first 10 years after surgery. A randomized study is needed to confirm these results.