Prospective angiography in the Bypass Angioplasty Revascularization Investigation trial indicated a 91.6% 1-year patency (< 50% stenosis) for left internal mammary artery (LIMA) grafts. The atherosclerosis of LIMA grafts is rare, and the long-term patency rate of left LIMA-to-left anterior descending (LAD) coronary artery grafts is approximately 90% [1, 2].

The high patency of the LIMA-to-LAD graft also leads to an improved clinical outcome. Extensive observational studies showed that patients who received a LIMA-to-LAD graft had a better survival, and experienced fewer adverse cardiac events as compared to patients who received only saphenous venous grafts (SVGs) [3, 4].

However, there are increasing reports of LIMA graft failure due to diffuse narrowing.

Barner described the longitudinal thinning of IMA grafts in 1974, referring to it as "disuse atrophy", because the native coronary arteries to which the IMAs were anastomosed appeared to be patent and to have good flow [5]. Several years later, Geha and Bane reported the "distal thread phenomenon" in 2% of IMA grafts 13 months after coronary artery bypass grafting (CABG) [6], correlating it with grafts applied to mildly stenotic recipient coronary arteries. This type of LIMA graft failure was referred to widely as "string phenomenon".

The most common cause of the distal narrowing phenomenon appears to be grafting of the LIMA to a coronary artery with noncritical stenosis (< 50%), but several other causes for this phenomenon have been emerged, including damage during harvesting and mobilization of the LIMA, spasm, inflammation as part of a post-pericardiotomy syndrome or a steal phenomenon arising from a large undivided proximal branch of the LIMA [7, 8].

CABG to moderately stenotic target vessels may lead to competitive flow between the native vessel and the graft. Because of individual variations in the effects of stenotic lesions on the coronary flow during resting and exercise conditions and variations in the ability of the LIMA graft to adapt to the flow requirements, there is some controversy as regards the implication of competitive flow on the patency of LIMA bypass grafts [9–11].

Our present aim was to investigate the frequency of string sign of LIMA grafts in a series of patients 2-4 years after bypass surgery and to analyze the cases with regard to the role of competitive flow.

Six of the 105 patients (6%) exhibited diffuse involution of the graft (string sign). These cases were analyzed individually.

Case 1

A 60-year-old male patient who had participated in CABG 4 years previously (LIMA-LAD, SVGA-RCA) underwent repeated coronary angiography because of chest pain and a positive stress test. The angiography revealed an unligated thick side-branch of the left mammary artery with a high run-off, which probably contributed to the string sign of the main branch of the mammary graft (Figure 1). The possibility of an intervention for the occlusion of the side-branch arose, but the significance of the original LAD lesion was questionable, and the patient later became free of angina due to aggressive medical therapy.

Case 2

A 62-year-old male, who had undergone bilateral mammary bypass grafting on the LAD and the right coronary artery (RCA) 4 years earlier. Coronary angiography showed an almost occluded LIMA graft (string sign) (Figure 2A) with 50-60% stenosis on the proximal part of the LAD (Figure 2B). The anatomosis of the right IMA graft displayed a high-grade stenosis. The previous myocardial scintigraphy revealed a reversible perfusion defect on the inferior wall, while pressure wire measurement on the LAD proved that the lesion of the LAD was not associated with a significant pressure gradient even during vasodilatation (FFR = 0.83) (Figure 3), suggesting sufficient remaining (competitive) flow in the native LAD. A stent was implanted in the right IMA-RCA anastomosis, after which the patient's symptoms improved.

Case 3

A 61-year-old man after an inferior myocardial infarction underwent surgical revascularization involving a LIMA graft on the LAD and a venous graft on the aberrant left circumflex artery (LCx) from the right Valsalva sinus. One year later, the repeated coronary angiography detected string sign of the LIMA graft (Figure 4.) and total occlusion of the venous graft. Despite the 57% diameter stenosis of the LAD lesion (Figure 5.), pressure wire measurement excluded a hemodynamically significant lesion in this coronary artery. The aberrant LCx lesion was treated percutaneously by stent implantation.

Case 4

Five years after the bypass operation (LIMA-LAD, SVGA-1^st obtuse marginal branch (OM), -RCA), a 65-year-male patient was recatheterized because of the recurrence of angina-like symptoms. The venous grafts were occluded, while the LIMA graft was widely patent, with an intermediate lesion in the run-off under the anastomosis of the LIMA. A total arterial revascularization redo operation was decided on, and radial grafts were applied on the LAD, OM and RCA. After 3 years repeated coronary angiography revealed the string sign of the previously patent LIMA graft because the competitive flow of the new radial graft supplied the LAD more intensively than the previous LIMA graft (Figure 6).

Case 5

Three years after the bypass surgery (LIMA-LAD, SVGA-1^st diagonal, -1^st OM and -RCA), a 75-year-old man underwent recatheterization because of angina-like symptoms. Coronary angiography showed the string sign of the LIMA graft, while the venous grafts were patent (Figure 7). The originally severe lesion demonstrated such a degree of regression that the flow in the LAD improved to a normal level, resulting in competition of the LIMA graft.

Case 6

A 56-year-old male patient had presented with unstable angina 3 years previously. Angiography revealed three-vessel disease with occlusion of the RCA and the LCx. In the middle region of the LAD, there was a tight lesion, and the orifice of the diagonal branch exhibited a mild lesion. The patient underwent bypass grafting: the LCx and the RCA received radial artery grafts, while the diagonal branch and the LAD were sequentially grafted by the LIMA. The patient made a good recovery from surgery, and was free of symptoms for more than 2 years. The index admission of the patient was necessary because of recurrence of the angina. The repeated angiography demonstrated patent radial grafts to the RCA and the LCx, but the LIMA graft was occluded proximally and did not fill the diagonal branch. Only the short distal part of the LIMA graft was open, connecting the proximal part of the LAD to the distal segment through the diagonal branch (Figure 8). It was decided to perform an intervention on the LAD lesion with stent implantation in order to improve the flow in the distal LAD.

Internal mammary arteries are the grafts of choice for CABG because they are generally free of atherosclerosis and exhibit high patency rates as grafts. Despite the overall excellent patency rates, however diffuse or distal narrowing of IMA grafts, the string phenomenon, occurs with appreciable frequency, and ultimately leads to graft failure [5–8].

It has been shown that CABG to minimally and moderately stenotic target vessels may lead to competitive flow between the native vessel and the graft. Competitive flow is a multifactorial phenomenon, and even an estimate of its impact is difficult, especially if based on preoperative coronary angiography alone [9, 10].

There is a significant body of clinical evidence suggesting that the size of the IMA is reduced under competitive flow conditions, and this can result in IMA graft failure. The study by Pagni et al. implicated two factors that could potentially lead to the development of IMA graft failure: retrograde systolic flow and low diastolic flow. Endothelial signals may modulate downsizing of the vessel diameter when faced with either or these stimuli [14].

Our series of patients was found to include 6 cases with the string sign of the LIMA. Angiography indicated competitive flow in all 6 cases as a cause of the development of the failure of the LIMA graft. In the cases without redo graft on the LAD, QCA measurement revealed 31-57% diameter stenosis in the LAD proximally to the LIMA graft. In 2 patients, we performed FFR measurements to confirm the nonsignificance of the LAD lesions. The FFR values (0.83 and 0.89) excluded s significant flow limitation of the stenoses. Of the 6 cases demonstrating the string sign, 3 (50%) had nonsignificant stenosis according to the FFR or QCA criteria.

The FFR (calculated from coronary artery pressure measurements) has been shown to be an accurate and lesion-specific index for determining if an intermediate stenosis is functionally significant and responsible for reversible ischemia. A threshold value of 0.75 clearly distinguishes lesions responsible (FFR < 0.75) or not responsible (FFR ≥ 0.75) for reversible ischemia during exercise. On the basis of the published data, our observations are in line with the value of the functional assessment of lesion severity by FFR measurement as a potential guide for a decision concerning grafting of an intermediate lesion [15].

In 3 cases, we identified relatively rare sources of the competitive flow in the background of the string sign: a new radial graft on the LAD, significant regression of the LAD lesion, and a sequential LIMA graft to the diagonal branch without a significant lesion.

Even though previous observations did indicate clinical relevance of an occluded bypass graft on a nonsignificant lesion, we consider that careful analysis of the clinical scenarios is mandatory for a correct decision regarding grafting: an operation that is too early may lead to the inappropriate use of grafts without prevention of the consequences of the future progression of the disease.

Written informed consent was obtained from patients.