Quin J, Lucke J, Hattler B, Gupta S, Baltz J, Bishawi M, Almassi GH, Grover FL, Collins J, Shroyer AL. Surgeon Judgment and Utility of Transit Time Flow Probes in Coronary Artery Bypass Grafting Surgery. JAMA Surg. 2014;149(11):1182-1187. doi:10.1001/jamasurg.2014.1891
Transit time flow (TTF) probes may be useful for predicting long-term graft patency and assessing grafts intraoperatively in patients undergoing coronary artery bypass grafting (CABG); however, studies of TTF probe use are limited.
To examine 1-year graft patency and intraoperative revision rates in patients undergoing CABG based on intraoperative TTF assessment.
Design, Setting, and Participants
Retrospective analysis of a multicenter randomized clinical trial conducted at 18 Veterans Affairs hospitals using the Randomized On/Off Bypass (ROOBY) Trial data set. Of the original 2203 patients undergoing CABG surgery with or without cardiopulmonary bypass from February 1, 2002, through May 31, 2008, we studied a subset of 1607 who underwent TTF probe analysis of 1 or more grafts during surgery.
Use of TTF probes to assess graft flow and pulsatility index (PI) values. The decision to revise a graft was based on the judgment of the attending surgeon.
Main Outcomes and Measures
Rates of 1-year FitzGibbon grade A patency and intraoperative revision were compared based on TTF measurements (<20 [low flow] vs ≥20 mL/min [normal flow]) and PI values (<3, 3-5, and >5).
We measured TTF and/or PI in 2738 grafts, and 1-year patency was determined in 1710 (62.5%) of these grafts. FitzGibbon grade A patency occurred significantly less often in grafts with a TTF with low flow (259 of 363 [71.3%]) than in those with normal flow (1174 of 1347 [87.2%]; P < .01). FitzGibbon grade A patency was also inversely correlated with increasing PI values, as found in 936 of 1093 grafts (85.6%) with a PI less than 3, 136 of 182 grafts (74.7%) with a PI of 3 to 5, and 91 of 134 grafts (67.9%) with a PI greater than 5 (P ≤ .01). Intraoperative graft revision was more frequent in grafts with low flow (44 of 568 [7.7%]) than in those with normal flow (8 of 2170 [0.4%]; P < .01). Graft revision was also more frequent as PI increased (12 of 1827 [0.7%] with a PI <3, 9 of 307 [2.9%] with a PI 3-5, and 9 of 155 [5.8%] with a PI >5; P < .01).
Conclusions and Relevance
Intraoperative TTF probe data may be helpful in predicting long-term patency and in the decision of whether to revise a questionable graft for patients undergoing CABG surgery.
Unlike perioperative mortality risk, which has steadily improved over time,1,2 graft patency after coronary artery bypass grafting (CABG) has not changed significantly. Reasons for the stagnation likely include suboptimal conduit or coronary anatomy; however, non–patient-related factors might also contribute to early graft disease and warrant investigation. One such avenue of study involves the use of transit time flow (TTF) probes that calculate graft flow based on the travel time differential between 2 opposing ultrasonographic beams.3 The TTF probes have been studied as a means to assess intraoperative and long-term graft patency.4
The purpose of this investigation was to add to the current literature by providing data on probe use from within the Randomized On/Off Bypass (ROOBY) Trial.5 This retrospective study of the ROOBY data examined the following: frequency of TTF probe use within the ROOBY Trial, intraoperative flow and pulsatility index (PI) values, intraoperative revision rates with prerevision and postrevision flow and PI values, and 1-year graft patency6 rates for the subset of grafts that underwent assessment with cardiac catheterization. We hypothesized that graft flow and PI values would correlate with 1-year graft patency and intraoperative revision rates and that flow and PI would improve after graft revision. To guide future intraoperative decision making, literature-based flow and PI thresholds were identified a priori, with the utility of TTF and PI measures evaluated using standard diagnostic test performance metrics.
Data from the Veterans Affairs Cooperative Studies Program (No. 517) study, also known as the ROOBY Trial, were used for this analysis. The ROOBY Trial protocol and associated supplemental analyses, which were coordinated by the executive committee of the Cooperative Studies Program 517, were approved by the institutional review boards and research and development offices of each participating Veterans Affairs (VA) Medical Center. Each participating patient provided written informed consent and signed a Health Insurance Portability and Accountability Act authorization before the start of data collection. Details of patient recruitment, randomization, and data collection were published previously.5
In brief, from February 1, 2002, until May 31, 2008, 2203 patients who needed elective or urgent CABG at 18 participating VA medical centers were randomized to the technique with (on-pump) or without (off-pump) cardiopulmonary bypass. The original study end points included 1-year all-cause mortality, nonfatal myocardial infarction, and repeated coronary revascularization. Patients were asked to return at 1 year for cardiac catheterization because graft patency was a major secondary end point of the study. Of the 2203 enrolled veterans, 1370 (62.2%) returned for follow-up angiography.
Within the ROOBY Trial, intraoperative graft flow and PI were assessed using 1 of 2 commercially available TTF probes (Transonic Systems, Inc, or Medtronic, Inc). Whether to use the probe and the method of graft assessment was left to the discretion of the individual surgeon, as was the decision of whether to revise a questionable graft. Patients undergoing on-pump CABG underwent graft flow and PI assessment after separation from bypass. All final graft flow and PI assessments were recommended to be performed after the patient’s heparin therapy was reversed. Only single-outlet grafts were included in this analysis; sequential grafts and T-grafts were excluded. Data for this analysis were collected from July 1, 2003, through May 31, 2008.
Flow and PI were analyzed separately and independently of each other. Based on the literature, the following 2 TTF groups were compared: grafts with an initial TTF less than 20 mL/min (low-flow group) vs 20 mL/min or greater (normal-flow group). Three groups with PI values less than 3, 3 to 5, and greater than 5 were compared because the literature is divided as to whether greater than or equal to 3 vs greater than 5 is an indication of abnormal pulsatility. Revision rates were compared using a χ2 test for the 2 TTF and 3 PI groups.
Graft patency was graded using the FitzGibbon classification system in which grade A was an excellent/unimpaired graft and grade O was an occluded graft.6 Grafts undergoing intraoperative revision were analyzed according to their postrevision TTF and/or PI when these indices were remeasured after graft revision; otherwise, they were analyzed according to their prerevision flow and PI values. For example, a graft in which postrevision flow improved from 15 to 40 mL/min was included in the normal-flow group for the patency analysis.
For the grafts that underwent revision, the mean flow was calculated before revision and compared with the mean flow after revision. Last, the sensitivity, specificity, and positive and negative predictive values of using the TTF probe as a test to predict graft patency were calculated using a TTF less than 20 mL/min, a PI greater than or equal to 3, and a PI greater than 5. For all analyses, we used P < .01 to avoid a potential multiple comparisons challenge. Statistical analyses were performed by the VA Cooperative Studies Program Coordinating Center at Perry Point, Maryland, using commercially available software (SAS, version 9.2; SAS Institute Inc).
Within the 18 participating VA medical centers in the ROOBY Trial, use of the TTF probe varied widely. Twelve VA study sites used the probe in most cases, 3 used it in about one-third of cases, and 3 used it sparingly or not at all. Patient characteristics of the 1067 patients who underwent evaluation of at least 1 graft with the TTF probe are presented and compared with the 501 ROOBY patients who were known not to have undergone TTF probe use (Table 1). Except for a few patient risk factors (chronic obstructive pulmonary disease and smoking status [both, P = .02] and myocardial infarction status [P < .01]), the patients who underwent TTF assessment were similar to those who did not.
The TTF data were initially examined separately within the on-pump and off-pump patient groups and, because the within-group results were comparable to the combined cohort results, both groups were combined into a single cohort. Overall, 568 of 2738 grafts (20.7%) had low flow, with a revision rate of 44 of 568 grafts (7.7%) (Table 2). In comparison, the revision rate for grafts with normal flow was significantly less frequent (8 of 2170 [0.4%]; P < .01). For pulsatility assessment in 2289 grafts, the PI was less than 3 in 1827 (79.8%), 3 to 5 in 307 (13.4%), and greater than 5 in 155 (6.8%) (Table 3). Revision rates increased with increasing PI values, with the lowest rate of 0.7% in the group with a PI less than 3, which was significantly lower than the 5.8% rate in the group with a PI greater than 5 (P < .01).
Of 54 total revised grafts, 23 in situ left internal mammary artery (LIMA) and 24 saphenous vein grafts had prerevision and postrevision flow assessments. On average, significant improvements in flow were seen after revision for both conduit types. For in situ LIMA grafts, mean TTF improved from 8.9 mL/min before revision to 42.0 mL/min after revision (P < .01), whereas for saphenous vein grafts, mean flow improved from 10.2 to 25.6 mL/min (P < .01). The details of 27 revised grafts with complete prerevision and postrevision TTF and PI assessments are presented in Table 4, which includes the type of conduit, target artery, and FitzGibbon 1-year patency grade.
Overall, of the 2738 grafts undergoing assessment by TTF probe, 1710 (62.5%) had patency determined with 1-year catheterization. The rate is consistent with the overall 1-year angiography rate in the ROOBY Trial of 62%.5 FitzGibbon grade A patency was significantly less frequent in 259 of 363 low-flow grafts (71.3%) compared with 1174 of 1347 normal-flow grafts (87.2%; P < .01). For the in situ LIMA grafts, 116 of 141 in the low-flow group (82.3%) had FitzGibbon grade A patency compared with 410 of 429 in the normal-flow group (95.6%; P < .01). Among the saphenous vein grafts, 121 of 195 low-flow grafts (62.1%) and 684 of 823 normal-flow grafts (83.1%) had FitzGibbon grade A patency (P < .01). For the 3 PI categories less than 3, 3 to 5, and greater than 5, 936 of 1093 grafts (85.6%), 136 of 182 (74.7%), and 91 of 134 (67.9%), respectively, had FitzGibbon grade A patency (P < .01).
Calculations for the sensitivity, specificity, and positive and negative predictive values of the probe for predicting graft occlusion using threshold flow values of less than 20 mL/min, a PI greater than or equal to 3, and a PI greater than 5 are presented in Table 5. The sensitivities of all 3 factors were low at less than 40%. Specificities were high and improved from 80.0% using a PI greater than or equal to 3 to 92.0% using a PI greater than 5. The TTF and PI assessments had low positive predictive values but high negative predictive values for 1-year graft occlusion.
Compromised graft patency continues to limit the immediate and long-term success of CABG surgery; as such, further investigation of methods to predict and improve patency is necessary. Recently, interest in the intraoperative use of TTF probes as a means of assessing flow and predicting the patency of grafts has increased. Potential advantages of probe use include their relative ease of use and reproducibility, their potential for identifying and correcting compromised grafts in the operating room,7- 9 and the potential for predicting long-term graft patency.7 Given that a significant number of patients in the ROOBY Trial underwent TTF probe use during surgery, most of whom underwent 1-year catheterization, this retrospective study sought to add to the current literature by examining the correlation of TTF values with intraoperative revision rates and 1-year graft patency.
The current literature suggests that TTF measurements less than 15 to 20 mL/min are low.10,11 Equally important in the determination of graft integrity is the PI, which is measured as the difference of maximum and minimum flow divided by the mean flow. Although a PI cutoff greater than 5 traditionally has been used as an indicator of questionable graft integrity,12- 14 a PI threshold of 2.5 to 3.0 may provide better detection of potentially compromised grafts.3,15
Studies of TTF probe use with angiographic follow-up are few and have shown conflicting results. For example, the study by Tokuda et al15 of 104 grafts in 51 patients who underwent catheterization 1 to 4 years after surgery demonstrated a correlation between PI value and angiographic patency with a mean PI of 2.75 in widely patent grafts compared with a mean PI of 4.03 in grafts that showed compromised flow. By contrast, Hol and colleagues16 studied 67 LIMA grafts and 57 saphenous vein grafts in 72 patients undergoing CABG. Intraoperative and 1-year follow-up angiography was performed. The investigators found no correlation of PI or TTF values with FitzGibbon patency based on intraoperative findings and 1-year angiograms. Similarly, a randomized study by Singh and colleagues17 of 156 patients undergoing CABG randomized to intraoperative graft assessment vs no assessment found that routine intraoperative assessment of grafts did not affect patency rates.
In the present study, a flow value of 20 mL/min or greater was used to distinguish normal from low flow. The rate of FitzGibbon grade A patency of 87.2% in the normal-flow group was significantly better than the rate of 71.3% in the low-flow group. In comparing the 3 PI categories, patency diminished as the PI value increased. The FitzGibbon grade A patency of 85.6% in the group with PI less than 3 was significantly better compared with graft patency in the groups with PI of 3 to 5 (74.7%) and PI greater than 5 (67.9%). These results may support using a threshold PI value of 3 or greater when considering whether a graft may have compromised flow.
However, TTF data must be interpreted with caution. As anticipated by the high percentage of patent grafts within the low-flow or high-PI groups, the ability of the probe to detect eventual graft occlusion is poor, with positive predictive values ranging from 23.1% to 27.6% depending on the measurement variable. However, the negative predictive values are higher, ranging from 87.8% to 90.3%. As evident from Table 4, some of the grafts that were revised had initial TTF readings that indicated adequate flow; as such, additional factors were likely considered by the surgeons in the decision to revise these grafts. Because many of the grafts with improved postrevision flow were in situ LIMA grafts, this approach appears to have potential clinical usefulness. Ultimately, graft patency is likely dependent on multiple factors, such as patient comorbidities, type of conduit used, target vessel size, and degree of target vessel disease. For example, in this study, the mean (SD) target vessel size in low-flow grafts was 1.5 (0.4) mm, which was significantly smaller than the mean (SD) of 1.7 (0.4) mm in normal-flow grafts. Confounders like these are a major limitation of this study and other studies of TTF use and help to explain the poor predictive value of TTF measurements and the variation in surgeon judgment as to when to revise a graft despite flow measurements. As such, although we would not discourage routine use of the TTF probe in patients undergoing CABG, we hesitate to recommend that this technique be adopted as standard practice, as has been advocated by some investigators.7,9
Another limitation of this study is the initial lack of a standardized protocol for probe use and data collection until a policy for flow meter use was initiated approximately 1 year after study start-up. Guidelines for the policy for flow meter use included taking flow measures after the patient was removed from bypass with a diastolic blood pressure documented to range from 50 to 70 mm Hg and final flow measurements after the reversal of heparin therapy. Some of the differences in TTF and PI values might result from variation in the technique of measurement rather than actual graft integrity.
Surgeon judgment was used in deciding when and how to use the probe. Because not all grafts were studied, a selection bias for the type of grafts that underwent TTF measurement may be present; for example, a surgeon may have decided not to assess a graft that was not technically revisable because of poor substrate. Only about half of revised grafts underwent remeasurement of TTF and PI values, which may have also introduced bias in the comparison of pre- and post-TTF values. Sequential grafts and T-grafts were not included in this analysis to simplify interpretation of angiographic findings; however, the number of these grafts was small and unlikely to have altered interpretation of results. Counterintuitively, some of the grafts that were revised did not have TTF readings to indicate a poor graft and did not improve after revision. On closer review of these grafts, no unifying factor indicated why the revision was undertaken. Reasons for revision might have been recorded in the data collection; an example would be a graft with good flow but excessive length. Last, given that the VA population is mostly male, the results are likely not applicable to women.
Limitations notwithstanding, this analysis suggests that intraoperative TTF findings have predictive value in determining eventual graft patency. The routine use of TTF probes might also prompt consideration of graft revision in cases in which the PI is abnormal or flow is much lower than expected to avoid the poor outcome of incomplete revascularization. However, because graft patency is determined by a variety of factors, some of which are not modifiable, the decision for TTF probe use and graft revision may be best left to individual surgeon judgment. Additional research, however, appears warranted to identify how best to use TTF findings to guide future graft-specific decisions, optimize long-term graft patency, and improve overall patient clinical outcomes.
Accepted for Publication: July 7, 2014.
Corresponding Author: Jacquelyn Quin, MD, Surgery Service, Veterans Affairs Boston Healthcare System, 1400 VFW Pkwy, Mail Code 112, West Roxbury, MA 02132 (email@example.com).
Published Online: September 24, 2014. doi:10.1001/jamasurg.2014.1891.
Author Contributions: Dr Collins had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Quin, Lucke, Baltz, Bishawi, Grover, Collins, Shroyer.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Quin, Lucke, Almassi, Grover, Shroyer.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Grover, Collins.
Obtained funding: Grover, Shroyer.
Administrative, technical, or material support: Quin, Gupta, Baltz, Almassi, Grover, Collins.
Study supervision: Lucke, Hattler, Grover, Collins, Shroyer.
Conflict of Interest Disclosures: Dr Almassi receives research nurse salary support from Eli Lilly & Company. No other disclosures were reported.
Funding/Support: This study was supported by the Cooperative Studies Program (CSP) of the Department of VA Office of Research and Development.
Role of the Funder/Sponsor: The CSP of the VA Office of Research and Development, as related to the VA CSP 517 Randomized On/Off Bypass (ROOBY) Trial, provided support for the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.
Previous Presentation: This paper was presented at the 38th Annual Surgical Symposium of the Association of VA Surgeons; April 6, 2014; New Haven, Connecticut.
Additional Contributions: Annette Wiseman provided technical and administrative assistance. XiaoLi (Shirley) Lu, MPH, provided statistical analysis. Both are affiliated with the Cooperative Studies Program at Perry Point, Maryland; neither received financial compensation aside from salary.