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Ann Thorac Surg 2004;77:1542-1549
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

First-year outcomes of beating heart coronary artery bypass grafting using proximal mechanical connectors

^a Cardiopulmonary Research Science and Technology Institute, Dallas, Texas USA
^b Department of Clinical Research, Medical City Dallas Hospital, Dallas, Texas, USA

Accepted for publication September 18, 2003.

^* Address reprint requests to Dr Dewey, 7777 Forest Ln, Suite A323, Dallas, TX 75230, USA
e-mail: tdewey{at}csant.com

Presented at the Poster Session of the Thirty-ninth Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2003.

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
BACKGROUND: To determine the extended results of mechanical connectors we compared the 1-year outcomes of patients having beating heart coronary artery bypass surgery with at least one sutured or mechanically connected proximal vein graft anastomosis.

METHODS: From May 2001 to December 2001, 166 patients were identified as having undergone off-pump bypass grafting utilizing at least one St. Jude symmetry aortic connector (St Jude Medical Anastomotic Technology Group, St. Paul, MN). Follow-up for major adverse cardiac events (MACEs), which is defined as cardiac mortality, myocardial infarction, or revascularization of a previous target vessel, was obtained on 162 patients (97.6%). A control group of 159 patients was identified from a cohort of patients having beating heart surgery with one or more sutured proximal vein graft anastomosis in the preceding year. The MACE follow-ups were obtained in 136 patients (85.6%) by direct telephone contact.

RESULTS: Patients with connectors showed an accelerated number of MACEs beginning approximately 180 days from the time of surgery and stabilizing at approximately 300 days. Logistic regression analysis identified the presence of diabetes as a significant preoperative risk factor predisposing patients to earlier onset of MACEs (p = 0.03) with an odds ratio of 2.9 (95% confidence interval, 1.1 to 7.6). Insulin dependent diabetics showed no differences between connector and control patients in the frequency or timing of MACEs. Connector patients using oral hypoglycemic agents demonstrated a significant deviation (p = 0.01) from a similar control population in the prevalence and timing of MACEs.

CONCLUSIONS: Connector patients showed an increased incidence of early MACEs. These events were characterized by an increased requirement for early target vessel revascularization and were predominantly in noninsulin-dependent diabetics.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Off-pump coronary artery bypass grafting has evolved in an attempt to decrease the morbidity and mortality associated with conventional coronary artery bypass grafting utilizing extracorporeal circulation. Traditionally a partial occluding clamp is placed on the ascending aorta in order to suture a proximal vein graft anastomosis in both on- and off-pump surgery. This technique, although familiar to all surgeons, exposes the patient to possible embolization of atheromatous debris from the aorta [1], as well as potential aortic dissection. Although numerous alternative techniques utilizing tubes, clips, staples, and glues have been used to anastomose vessels [2, 3, 4, 5, 6, 7], suturing remains the method by which all other approaches are measured. Anastomotic connectors have been developed as an enabling technology to facilitate the proximal anastomosis without the use of a partial occluding clamp. This innovative technology promises to: (1) standardize the quality of the proximal anastomosis, (2) reduce the technical demand of the anastomosis (especially in a minimally invasive approach), (3) avoid aortic cross clamping, and (4) expedite the procedure. Whereas success rates for aorto-saphenous vein graft anastomosis using mechanical connectors have been comparable with traditional methods in initial reports [8, 9, 10, 11], extended follow-up and outcomes have not been reported. In order to determine the extended results of mechanical connectors, we compared the outcomes of patients having beating heart coronary artery bypass surgery with either a sutured or mechanically connected proximal anastomosis for as many as 2 years.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Patient population
From May 2001 to December 2001, 166 patients were identified as having undergone off-pump bypass grafting utilizing a least one St. Jude symmetry aortic connector (St. Jude Medical Anastomotic Technology Group, St. Paul, MN). The Symmetry anastomotic device is a Nitinol connector (St. Jude Medical Anastomotic Technology Group) designed to create an anastomosis between the ascending aorta and a saphenous vein graft without the use of a partial occluding clamp. During the study period, 192 patients underwent off-pump coronary artery grafting, which made them potential candidates. Of this group, 166 patients (86%) received at least one connector; the rest of the patients were not included as candidates for a variety of reasons (all arterial grafts, no consent, and so forth). Follow-up for major adverse cardiac events (MACEs), which is defined as cardiac mortality, myocardial infarction, or revascularization of a previous target vessel, was obtained on 162 of 166 patients (97.6%) using direct telephone contact, communication with the patient's referring physician, or interrogation of the National Death Registry. This group had a total use of 331 proximal connectors (average, 2.04 per patient). Mean follow-up was 333 ± 132 days with a range of 2 to 568 days. Thirty-nine patients (25%) with 88 connectors underwent surveillance screening for anastomotic patency utilizing electron beam angiography approximately 6 months after surgery. Twenty patients (39 connectors) returned for cardiac catheterization due to recurrence of symptoms.

A control group of 159 patients was identified from a cohort of patients having off-pump beating heart surgery with one or more sutured proximal vein graft anastomosis in the preceding year. Follow-up for MACEs was obtained by direct telephone contact in 136 patients (85.6%) with a total of 253 proximally sutured vein grafts. Mean follow-up in the control group was 523 ± 146 days with a range of 111 to 760 days. Surveillance electron beam angiography was not performed in this group.

Statistical analysis
Data were collected on Excel spread sheets and read directly into the SAS 8.2 program (SAS Institute, Cary, NC) using dynamic data exchange. Analysis of categorical risk and outcome variables was performed with Fisher's exact test for 2 x 2 tables and the ² test for larger tables. Survival curves were calculated using Kaplan-Meier statistics, and the survival function was plotted against time to event. Stratified curves were compared using the log-rank test. All p values were considered statistically significant when less than or equal to 0.05.

The Kaplan-Meier survival curves plot the fraction of patients who are still surviving (ie, in this case, those who have not had a MACE) against time from the start of monitoring (date of bypass surgery). Each major adverse cardiac event causes the surviving fraction to decrease, with the size of the decrease at the time point dependent on the number of patients who are still in the study at that time. When the curve extends past a particular patient's length of follow-up, the patient becomes "right censored" and is not included in the calculation of survivors. As their follow-up increases, the time of censoring moves to the right, unless they experience an event, and therefore more patients are used in the calculation (at risk) at any time. This affects the size of the drop for any event. It needs to be remembered that at longer follow-up times when there are few patients, each drop is exaggerated in size. As more patients are available at longer follow-ups, the size of the drop for each event is decreased. In this study, the control group had approximately 1 year longer follow-up; therefore the changes seen at approximately 400 to 500 days in the connector group are much larger for each event (ie, fewer patients were followed for this long) than for the controls in which the patient follow-ups extended well beyond 600 days. Data for periods of less than 400 days are unlikely to change much, because adequate numbers of patients in both groups have passed this mark.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Although this was not a randomized trial, analysis of 26 categorical preoperative risk factors showed no significant statistical differences between the two groups (Table 1). Analysis of continuous variables showed that average age, ejection fraction, and The Society of Thoracic Surgeon's predicted risk of mortality (also known as PROM, which is the calculated risk of mortality [0 to 1] based on an algorithm of 30 variables determined to be predictive of mortality in coronary artery bypass surgery from the Duke Clinical Research Institute) were not statistically different between the two groups (Table 1). The perioperative outcomes (Table 2) were equivalent for each patient group. There were no increased incidences of operative mortality, perioperative myocardial infarction, blood product usage, stroke, or acute renal failure in the connector group as compared with the control group.

The results of the MACE evaluations for both cohorts are shown in Figure 1. The MACE curves are plotted as a function of the elapsed time period from surgery to the occurrence of an identifiable event. The MACEs for the purposes of this study include myocardial infarction, mortality, and target vessel revascularization. Mortality included all cardiac related deaths and those deaths caused by unidentifiable events. Patients with connectors show an accelerated number of MACEs that appear to begin around 180 days from the time of surgery and then plateau at approximately 300 days. The control group demonstrated a gradual accumulation of MACE-related occurrences over the entire time course. With extended follow-up, the control group approached the connector group, and no statistically significant differences are seen between the two cohorts. Separating MACEs into individual components demonstrated that the predominant factor for the accelerated number of early occurrences in the connector group was a need for target vessel revascularization. The control group showed a more gradual accrual of interventions to a target vessel.

View larger version (23K): [in this window] [in a new window]   Fig 1. Major adverse cardiac event (MACE) occurrence in control and connector patients. (R. = right.)

Subgroup analysis for MACEs in 101 nondiabetic connector and 84 control patients demonstrated nearly identical accumulation of events (Fig 2). However, when MACEs in diabetic patients only were examined, an accelerated accumulation of occurrences were once again identified in the connector cohort (Fig 3). Furthermore, this deviation from the diabetic control group was more pronounced than when the connector and control groups were compared as a whole. Within the connector cohort only, diabetics demonstrated a greater number of events than nondiabetic patients (ie, 12 events in 61 patients [19.7%] vs 10 events in 101 patients [9.9%; p = not significant]). Alternatively, diabetics in the control group showed no predilection for increased events compared with nondiabetics (ie, 9 events in 51 patients [17.6%] vs 12 events in 84 patients [14.3%; p = not significant]).

View larger version (22K): [in this window] [in a new window]   Fig 2. Major adverse cardiac event (MACE) occurrence in nondiabetic patients. (R. = right.)

View larger version (22K): [in this window] [in a new window]   Fig 3. Major adverse cardiac event (MACE) occurrence in diabetic patients. (R.= right.)

View larger version (20K): [in this window] [in a new window]   Fig 4. Major adverse cardiac event (MACE) occurrence in insulin-dependent diabetic patients. (R. = right.)

View larger version (20K): [in this window] [in a new window]   Fig 5. Major adverse cardiac event (MACE) occurrence in diabetic patients controlled by oral medication. (R. = right.)

Twenty patients in the connector population had recurrence of symptoms during the study period and underwent repeat cardiac catheterization. Nineteen occluded target arteries were identified, nine in patients with diabetes. Twelve patients (with 15 occlusions of 23 connectors), underwent percutaneous intervention with stent placement in target arteries previously bypassed by a saphenous vein. Two patients (with four occlusions of four connectors) underwent redo-coronary artery bypass grafting. Four patients (with five occlusions of eight connectors) received medical therapy, and 2 patients (4 connectors) had negative angiograms.

To ensure that the occlusions identified by electron beam angiography or traditional plane x-ray angiography were not caused by a learning curve associated with a new treatment modality, we examined the distribution of occlusions in relation to the time of surgery within the study period (Fig 6). Despite peaks in the percent of occlusions in June and August 2001, there is no distinct clustering of events early in the study period to suggest an associated learning curve.

View larger version (39K): [in this window] [in a new window]   Fig 6. Correlation of major adverse cardiac events and time of surgery.

View larger version (40K): [in this window] [in a new window]   Fig 7. Distribution of patients and connectors in study subsets. (EBA = electron beam angiography; MACE = major adverse cardiac events).

	Comment

Top Abstract Introduction Material and methods Results Comment References

This study demonstrates that in comparison with an equivalent control group, patients that received anastomotic connectors had an increased incidence of early MACEs. The majority of the events were related to the need for target vessel intervention. Multiple factors may negatively impact graft survival and freedom from target vessel reintervention, including technical problems at the time of surgery, poor quality conduit, diminished distal vessel run off, and progression of native vessel disease. A gradual decline of saphenous vein graft patency over time is an expected result of bypass grafting. FitzGibbon and colleagues [13] demonstrated that the early, 1-year, and 5-year patency rates for vein grafts was only 90%, 83%, and 74%, respectively. Technical issues related to the use of connectors that may negatively impact graft patency include the requirement that the saphenous vein arise from the aorta at a 90° angle in order to avoid kinking, the arteriotomy in the aorta be circular and sized for the individual connector, and the proximal anastomosis precede the distal anastomosis. Transcending these technical obstacles is largely a matter of training and experience with the device.

In this study, early MACEs were most common in the patients with diabetes and significantly more frequent in patients on oral hypoglycemic medications as opposed to those on insulin. In fact, there were no observable differences in MACEs between the control group and the nondiabetic connector cohort or the connector patients on insulin. The cause of this predisposition for early MACEs to occur primarily in connector patients with diabetes is unknown, but it bears resemblance to results seen in this population with percutaneous coronary interventions.

Hyperglycemia is associated with numerous systemic effects, such as increased oxidative stress, enhanced leukocyte endothelial interaction, and glycosylation of lipoproteins and apolipoproteins that may impact graft patency [14, 15]. In addition, hyperglycemia is known to increase the intracellular concentration of the metabolite diacylglycerol, an activator of the enzyme protein kinase C [16, 17]. Activated protein kinase C can inhibit the expression of endothelial nitric oxide synthase, thus leading to impaired endothelial vasodilatory regulation. The protein kinase C can also augment cytokine induced tissue factor gene expression and procoagulant activity in endothelial cells [18], thereby increasing the production of proinflammatory cytokines and proliferation of vascular smooth muscle cells. Diabetes is also known to produce unique alterations of the coagulation and fibrinolytic systems that combine to produce a prothrombotic state. This enhanced thrombogenicity may directly impact early and long-term graft survival.

Diabetes is recognized to be an important risk factor for poor outcomes after percutaneous coronary interventions [19, 20]. Potential mechanisms include an up-regulated inflammatory response that may result in chronic constrictive remodeling, an allergic reaction to the metallic elements of the stent, or a device design that may increase the amount of stent induced vascular wall injury [1, 22, 23]. Re-stenotic lesions in diabetics after stenting are characterized by a collagen-rich matrix that suggests an accelerated fibrotic rather than a proliferative response to injury [24]. Current anastomotic connector technology is remarkably similar to that of percutaneous stents. Both devices cause local vascular wall injury, and are made of metal elements, a significant portion of which remains in the bloodstream.

We recently had the opportunity to explant two anastomotic connectors in a previously bypassed nondiabetic patient undergoing cardiac transplant. Grossly, both anastomoses were subtotally occluded at the ostia with patent distal saphenous vein. Histology of the specimens demonstrated necrosis in the area at which the vein wall abuts the aorta and fibrous tissue occluding the orifice of the anastomosis within the aorta (Fig 8A, 8B). These findings were indicative of an enhanced fibrotic reaction elicited by deployment of the connector. This response could be exaggerated by the procoagulant and proinflammatory predisposition of the diabetic patient, thus leading to reduced graft patency.

View larger version (120K): [in this window] [in a new window]   Fig 8. (Top) Low power view of occluded connector in the aorta. (A) Histologic section of occluded connector and fibrous tissue in the device. (B) Wall of vein graft. (C) Intimal surface of aorta. (D) Adventitial surface of the aorta (x10 magnification; higher power than of histologic section). (Bottom) High power view of same occluded connector in the aorta. (E) An area of necrosis in the wall of the vein graft. (F) One of the struts of the connector (x25 magnification).

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Todd M. Dewey Syma L. Prince James R. Edgerton Mitchell J. Magee Michael J. Mack Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dewey, T. M. Articles by Mack, M. J. Search for Related Content PubMed PubMed Citation Articles by Dewey, T. M. Articles by Mack, M. J. Related Collections Coronary disease