The String Phenomenon: An Important Cause of Internal Mammary Artery Graft Failure

Abstract

Internal mammary arteries are the grafts of choice for coronary artery bypass because they are generally free of atherosclerosis and they have high patency rates as grafts. There are, however, increasing reports of graft failure due to diffuse or distal narrowing, known as the string phenomenon.

From June 1999 to October 1999, we prospectively reviewed all cases of internal mammary artery angiography at our institution. Twenty-eight cases of internal mammary artery graft failure were identified (M:F, 15:13; mean age, 62 years) out of 261 patients who had undergone internal mammary artery grafting at any institution, including ours. The mean interval between coronary artery bypass and re-angiography was 35 months. There was evidence of competitive flow in 81% (22 of 27) of patients whose internal mammary grafts had developed the string sign.

This observational study supports the hypothesis that competitive flow predisposes internal mammary grafts to the string phenomenon. Given the high frequency of competitive flow situations amongst patients with internal mammary artery graft failure, caution should be exercised in the anastomosis of the internal mammary artery to recipient vessels that are less than severely stenosed.

The internal mammary artery (IMA) is the conduit of choice for coronary artery bypass grafting (CABG) because of its freedom from atherosclerosis when harvested and its high rate of long-term patency when grafted. ¹ Improved survival has been reported in patients who receive IMA grafts. ^2,3 To improve the results of CABG and to decrease the need for re-intervention, surgical practice indications have been extended to include the revascularization of coronary arteries with less-than-critical stenosis. ⁴

Despite overall excellent patency rates, we and others ^5–7 have noted increasing frequency of diffuse or distal narrowing of IMA grafts, the so-called “string phenomenon” that ultimately leads to graft failure. Various causes for this entity have been suggested, including damage during harvesting and mobilization, spasm, inflammation as part of a post-pericardiotomy syndrome, ⁷ or a steal phenomenon arising from a large undivided proximal branch of the IMA. ⁸

In the last 5 years, we have found several examples of IMA graft failure in patients with less-than-critical stenosis of the recipient artery, which suggests that competitive flow may cause the string phenomenon and subsequent graft failure. We undertook this study to further characterize this phenomenon and to test the hypothesis that competitive flow is instrumental in the development of the string phenomenon.

Patients and Methods

From June 1999 to October 1999, we prospectively reviewed the cine-angiograms of all patients who underwent angiography of the IMA at our institution during that time. A total of 288 IMA angiograms were performed on 279 patients. There were 261 postoperative IMA grafts and 27 ungrafted native IMAs. The 261 postoperative patients had undergone surgery at various institutions, including ours, and all the studies were performed for new or worsening symptoms or for cardiac events. Twenty-seven patients underwent IMA angiography before surgery in order to assess the suitability of the IMA for grafting, specifically to exclude subclavian obstruction. Cineangiograms in the postoperative patients were screened specifically for graft failure and competitive flow conditions. Competitive-flow conditions were defined as follows:

1. a recipient vessel with less-than-critical stenosis (<70%); or

2. a recipient vessel with a separate, alternative source of flow in the form of a patent vein graft from another coronary artery.

In some IMA grafts, another type of competition was noted: steal by an unligated proximal branch of the IMA. We also reviewed earlier angiograms and hospital records to assess timing of surgery and severity of stenosis before CABG. Both authors viewed all angiograms.

Results

Figure 1 presents our findings in diagrammatic form. The IMA grafts were patent in 233 of the 261 instances (89.3%). Twenty-eight cases (10.7%) of IMA failure were identified for study. Of these patients, 15 were male, and 13 were female. The mean age was 62 ± 11 years. The time interval between surgery and re-angiography in these 28 patients was 35 ± 35 months (range, 4 to 132 months). The reasons for postoperative angiography were recurrent chest pain (n = 25), acute myocardial infarction (n = 2), and evaluation before reoperation (n = 1).

Fig. 1 Diagrammatic summary of results.

In 1 of the 28 patients, inadvertent ligation of the IMA during harvesting was known to be the cause of the IMA failure. The remaining 27 developed the string sign. Out of the 27 patients with the string sign, 22 grafts (81%) had been implanted under competitive-flow conditions. Competitive flow was from at least one of the following sources, which are not mutually exclusive: a native coronary artery (n = 19); a patent vein graft to another coronary artery with unimpeded flow to the IMA-recipient artery (n = 4); and steal by unligated proximal branches of the mammary artery (n = 2) (Figs. 2, 3, and 4). In 18 cases, even though the IMA was anastomosed to a recipient artery under competitive-flow conditions, the string sign did not develop. Five patients who had received implants under non-competitive conditions developed the string sign. One such case was a surgical complication; the others resulted from anastomosis to a vessel with poor distal runoff (n = 4).

Fig. 2 A) Cineangiogram in the right anterior oblique projection demonstrates non-occlusive disease in the left anterior descending (LAD) artery. Note the string-like appearance of the IMA graft remnant (arrow). B) Cineangiogram in the antero-posterior projection shows the IMA string phenomenon.

Fig. 3 Cineangiogram in the antero-posterior projection shows a saphenous vein graft to the diagonal with unimpeded flow to both the diagonal and the left anterior descending coronary arteries. The string phenomenon of the internal mammary artery (not shown) was observed in this patient.

Fig. 4 Cineangiogram in the antero-posterior projection shows the string sign in the setting of possible steal from a large unligated proximal branch of the internal mammary artery (IMA). The string sign is present only in the distal segment of the IMA, beyond the unligated branch, which is away from the heart and supplies only the chest wall.

Discussion

We cannot comment on IMA patency rates because patients in our series were not studied electively after IMA grafting. Furthermore, our patient population was selected chiefly because of recurrent symptoms. The 10% IMA failure rate we noted at 3 years after CABG would not be unusual in such a group. However, the IMA string phenomenon was responsible for an inordinate number of these failures, and in 22 of 27 cases (81%) either the recipient vessel had adequate flow from a competing source, or an unligated branch was competing with the recipient artery.

Barner ⁵ first described longitudinal thinning of IMA grafts in 1974. He referred to this as “disuse atrophy” because the native coronary arteries to which the IMAs were anastomosed appeared to be patent and to have good flow. Several years later, Geha and Baue 6 described the “distal thread phenomenon” in 2% of IMA grafts at 13 months post-CABG. They correlated this with anastomosis of the graft to a marginally stenotic recipient coronary artery. Collectively, these variants have come to be known as the “string phenomenon.”

Various other causes for this phenomenon have been proposed. Spasm and inflammation of the IMA graft from a post-pericardiotomy syndrome have been suggested. ⁷ However, the notable lack of the string sign on the other IMA in cases with bilateral IMA grafts strongly argues against this. Damage to the IMA during mobilization and anastomosis (surgical complication) ⁷ can cause occlusion and focal distal narrowing, but this does not explain the diffuse pattern of the string phenomenon. Another possible reason is a steal phenomenon in which failure to ligate proximal branches of the IMA results in diminished flow after the bifurcation. ⁸ However, some series on the gastroepiploic arteries, which frequently have undivided proximal branches, have not shown an increased incidence of the string sign, suggesting that other factors must be at play. ⁹

Perhaps the most tenable theory is that of competitive flow. Under these circumstances, thinning of the grafts would appear to be a physiologic response to reduced blood flow. The decrease in caliber maintains the velocity of blood flow and, at least acutely, maintains patency. Siebenmann ¹⁰ described 10 cases of the IMA string sign; IMA grafts were bilateral in 6 cases and unilateral in 4. In all cases, the stenosis of the vessel bypassed was 50% or less. In the cases with bilateral IMAs, the contralateral IMA, anastomosed to a severely stenotic vessel, was widely patent. Hashimoto ¹¹ followed 30 IMA and 23 gastroepiploic artery grafts for a mean of 24 months. Stenosis of the recipient artery was significantly more severe in functioning grafts than in non-functioning ones (p <0.01). A linear regression model demonstrated that anastomotic graft narrowing and the degree of recipient coronary artery stenosis predicted graft patency.

There are dissenting opinions to the competitive-flow hypothesis. Competitive-flow conditions have been replicated in the canine model by anastomosing the IMA to a patent circumflex artery. ^12,13 Flow through the IMA graft, measured by electromagnetic flow probes, was maintained both acutely (immediately after) ¹² and long term (2 months). ¹³ Urschel ¹⁴ reported that intra-operative dilation of native lesions proximal to the IMA grafts had no adverse effects on graft patency 1–7 years later, despite competitive flow. Kawasuji and colleagues ¹⁵ performed follow-up on 100 patients with IMA grafts to the LAD. They found the string sign in only 3 of 14 patients whose IMA grafts were implanted under competitive-flow conditions. They concluded that IMA grafting was acceptable for a moderately stenotic artery. Their follow-up, however, was only 1 month.

Our study supports the hypothesis of competitive flow. Anastomosis of the IMA under such conditions appears to have been a factor in 81% (22 of 27) of our graft failures. The development of the string sign under non-competitive conditions (5 patients) suggests that this phenomenon may also occur in conjunction with anastomosis to a recipient vessel with poor distal runoff, and that, perhaps, the string sign is the “final common pathway” for long-term IMA failure. We must acknowledge that we did encounter 18 patent grafts in the presence of competitive flow. We cannot, however, comment on the frequency of graft patency or graft failure under competitive-flow conditions. A prospective study with elective postoperative angiography will be needed to answer that question.

This is only an observational study. The study population was of small size and was selected because of hospital presentation. Therefore, the true incidence of the string phenomenon in the presence or absence of competitive flow cannot be ascertained. Nevertheless, given the alarmingly high rate of IMA failure due to the string phenomenon, it is reasonable to recommend that caution be exercised in the anastomosis of the IMA to less than severely stenosed recipient vessels. A more detailed analysis of variables is clearly in order to further characterize this syndrome.