Discussion
The primary observation of this study is that the left ventricular systolic function in the NT-group is persevered at mean time 16 years. This is in line with our earlier findings by intravascular ultrasound,10 at 8.5 years that the process of atherosclerosis is delayed in the vein grafts prepared using the no-touch technique. The improved patency rate is the most likely cause of this preserved left ventricular EF in the NT-group as there were no difference between the two groups according to known cardiac risk factors including lipid status.
Compared with a well-known long-term follow-up study using mostly arterial revascularisation, Achouh et al14 reported a lower EF after 9.2 years, 55% compared to 56.7% preoperative, p=0.02.
The evaluation of the diastolic left ventricle function is very complex and can only be achieved clinically in less than one-half of patients,15 even in the hands of experts.16 ,17 In this study it is possible to obtain some indication of the diastolic function. Atrial size has been a surrogate for diastolic dysfunction in patients with normal left ventricular systolic function.18–21 Diastolic dysfunction has also been shown to predict atrial fibrillation.21 In this study the patients in the NT-group had a significantly lower left atrial size (p=0.034), the percentage of patients with a BNP ≥150 was lower in the NT-group and no patients in the NT-group suffered from atrial fibrillation versus 16.1% of patients in the C-group (p=0.021). This suggests a trend for a higher degree of diastolic dysfunction in the C-group.
Already by 8.5 years of clinical follow-up there were significantly more asymptomatic patients in the NT-group.9 At 16 years this pattern seems to continue, although not statistically significant and the comorbidities of the patients decrease the absolute benefit. The number of patients with recurrent angina was higher in the C-group and the number of patients suffering from an acute myocardial infarction was also doubled in the C-group, despite the fact that there was no difference between the two groups in the treatment of the known risk factors. The percentage of cardiac-related deaths was 12% in C-group and 8% in NT. However, there was no difference in PCI-revascularisation. We think that the issue of whether hard cardiac end points are influenced by NT vein grafting will be addressed in an ongoing multicenter study, where a larger number of patients will be studied. (SUPERIOR-SVG, clinicaltrials.gov: NCT01047449)
If we want to compare the clinical long-term results for the patients in the NT-group with total arterial revascularisation reported by others,22–24 we must make the comparison after approximately 8 years, the longest present follow-up for most all-arterial studies. The arterial revascularisation studies have shown a 7-year survival rate of 88–91% compared to 94% in group NT, freedom from cardiac death was 92–96% vs 100% in group NT, freedom from myocardial infarction 92–97% vs 98% in group NT, freedom from recurrent angina 85–92% vs 75% in group NT, freedom from any cardiac event 78–85% vs 74% in group NT. Puskas et al,25 showed that the use of bilateral internal thoracic artery had a significantly increased survival rate at 8 years compared to the usage of a single internal thoracic artery (89.3% vs 68.3%) irrespective the diabetic status of the patients. Achouh et al,14 had a total survival rate of 80% and a cardiac-related mortality of 7% after 9.2 years.
Locker et al,26 showed (in matched groups) a significantly better 15-year survival in the arterial revascularisation group compared to the LIMA+saphenous vein group (70% vs 60%). The cardiac-related mortality was not commented in this study. In our study the 16 years survival was 75% in NT and 73% in C with 8% and 12% cardiac-related mortality respectively.
It is well known that the treatment of the traditional risk factors after CABG is extremely important to slow down the atherosclerotic process in the vein grafts and the native coronary arteries. In this study we found at 16 years a low number of smokers, 10–15%, but the number of patients with hypertension, although treated, was as high as 20–30% and the amount of patients with elevated fasting β-glucose >6.1 mmol/L was high in both groups. This by definition is considered to be impaired fasting glycaemia and is a known risk for future development of diabetes and cardiovascular disease.
Probably the most important risk factor is the lipid levels. Despite a high number of patients treated with statins (94.6% in group NT-group and 86.5% in group C), the S-LDL levels were still elevated in both groups, (2.5–2.7 mmol/L). However, this was a significant improvement compared to the results from 8.5 years follow-up in the same study where the LDL level was 3.2–3.4 mmol/L. The percentage of patients reaching LDL ≤2.5 mmol/L was 53.9% in the NT-group and 61.3% in the C-group at 16-year follow-up, compared to only about 25% after 8.5 years. This improvement in lipid control is important since a previous post-CABG trial showed that aggressive reduction of LDL-cholesterol below 2.5 mmol/L, compared to moderate lowering to about 3.5 mmol/L, significantly reduced the progression of atherosclerosis in grafts.27 However, the accepted goal for optimal LDL-treatment according to European guidelines from 2010 in this category of patients is ≤1.8 mmol/L. This is obtained in 20–25% of the patients in both groups at 16-year follow-up.
We have no doubt that the preparation of saphenous vein grafts plays a vital role in the long-term result of CABG and that harvesting the grafts with the no-touch technique is a crucial step in that direction. This has even been mentioned in the latest ESC/EACTS guidelines 2014 on myocardial revascularisation, where the no-touch technique is recommended if the saphenous vein is harvested with an open technique.
Limitations of the study
The major limitation of this study is its small size. The study was initially designed to evaluate differences in graft patency between the NT-group and the C-group and not differences in the clinical or echocardiographic outcomes. Some preoperative baseline data were not available at the last follow-up and could not be accounted for in the final analysis. We also would like to mention that three patients in the NT-group and six in C-group did not perform the echocardiography at 16 years due severe comorbidities that hindered them from participating in the study. The statistical analysis was performed only on 34 patients in NT and 31 in C and did not account for the nine missing patients. We can only speculate that if the remaining very ill patients had been able to perform the echocardiography we would have obtained a lower EF for most of them with a bigger chance of increasing the differences between the groups (three in NT and six in C), that is, if the missing patients caused a bias it would probably favour the conventional group.
Some concerns have been raised about the conventional harvesting technique in this study. It is not unusual to dilate the saphenous vein to 300 mm Hg or more especially when dealing with small-caliber vessels with severe spasm after harvesting. A recent study showed a pressure rise under manual dilation of saphenous veins to >200 mm Hg in 29% of cases, >300 mm Hg in 16% of cases and >400 mm Hg in 21% of cases (the individuals performing the harvesting were totally blinded about the amount of pressure that was reached during distention 2).28 Another study mentioned that the saphenous veins are dilated to over 600 mm Hg before implantation.29 However, recent awareness of the mechanical damage caused by manual dilation has probably led to a more gentle approach during the preparation of the saphenous vein. In our study, the patency rate of the conventionally harvested veins was 89% after 1.5 years and 77% after 8.5 years.8 ,12 This is higher than what previously has been reported (10-years patency rate of the saphenous vein graft is about 40–60%).5