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We aimed to compare transit-time flow measurement (TTFM) parameters for on-pump (ONCAB) and off-pump (OPCAB) coronary artery bypass procedures.
The database of the Registry for Quality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery (REQUEST) study was retrospectively reviewed. Only single grafts were included (ie, no sequential or Y/T grafts). Primary end points were mean graft flow (MGF), pulsatility index (PI), diastolic fraction (DF), and backflow (BF). Unadjusted and propensity score-matching comparisons were performed.
Of 1016 patients in the REQUEST registry, 846 had at least 1 graft for which TTFM was performed. Of these, 512 patients (60.6%) underwent ONCAB and 334 (39.4%) OPCAB procedures. Mean arterial pressure (MAP) during measurements was higher in the OPCAB group. After propensity score-matching, 312 well balanced pairs were left. In these matched patients, MGF was higher for the ONCAB versus the OPCAB group (32 vs 28 mL/min, respectively, for all grafts [P < .001]; 30 vs 27 mL/min for arterial grafts [P = .002]; and 35 vs 31 mL/min for venous grafts [P = .006], respectively). PI was lower in the ONCAB group (2.1 vs 2.3, for all grafts; P < .001). Diastolic fraction was slightly lower in the ONCAB group (65% vs 67.5%; P < .001). The backflow was also lower in the ONCAB group (0.6 vs 1.3; P < .001) with trends similar to MGF and PI for venous and arterial grafts. There were 21 (3.3%) revisions in the OPCAB group and 14 (2.1%) in the ONCAB group (P = .198).
ONCAB surgery was associated with higher MGF and lower PI values, especially in venous grafts. Different TTFM cutoff values for ONCAB versus OPCAB surgery might be considered.
We sought to investigate if there is a difference in TTFM parameters between on-pump and off-pump CABG. We found that on-pump surgery was associated with higher mean graft flows and lower pulsatility indices, especially in venous grafts. Different TTFM cutoff values for on-versus off-pump bypass surgery might be considered.
Technological advances paved the way for the development of devices that can be used to assess grafts for intraoperative failure. Graft patency can be measured in various ways, but the most widespread technique is transit-time flow measurement (TTFM) because of its ease of use.
revealed a pooled rate of graft revisions of 4.3% per patient, and 2.0% per graft. In the grafts with an abnormal measurement, the pooled rate of graft revision was 25.1%. This frequency implies that there will be improvement in clinical outcomes with higher adoption rates and improved quality of intraoperative graft assessment,
However, these studies were limited by being either single-center series, by a relatively small sample size, or by type of grafts used and the parameters measured. If differences in flow rates do indeed exist, this discrepancy might suggest that there should be different thresholds for the TTFM parameters when evaluating graft quality in ONCAB versus OPCAB.
In this study, we sought to quantify differences in TTFM parameters for ONCAB and OPCAB using a retrospective review of the REQUEST trial—a large, multicenter cohort. Any existing differences could be used to help correlate successful procedures with specific cutoff values for each type of procedure, and eventually improve the quality of intraoperative decision-making in coronary artery bypass grafting (CABG).
REQUEST is an international, multicenter, prospective registry that enrolled 1016 patients in 7 cardiac surgery centers (4 in Europe and 3 in North America) between April 2015 and December 2017. Patients underwent isolated CABG with intraoperative assessment of multiple surgical sites, such as the ascending aorta (for cannulation, crossclamping, and proximal anastomoses, if any), coronary targets, conduits, and finally proximal and distal anastomoses, using high-frequency ultrasound and graft assessment using transit time flowmetry (TTFM) with the MiraQ or VeriQ C devices (Medistim ASA).
The registry was designed to capture information on any changes in the proposed surgical procedure on the basis of high-frequency ultrasound and/or TTFM findings. The results, along with the study protocol, were reported in a previous publication.
Institutional review board approval from each participating center was obtained before screening and enrollment. Informed consent was obtained from all enrolled patients (approval number for the various institutions: site 1: June 30, 2015 [15-63060-BO]; site 2: April 23, 2015 [REB15-0090]; site 3: August 6, 2015 [HS 053-15]; site 4: June 18, 2015; site 5: April 22, 2015 [15/SC/0194]; site 6: April 24, 2015 [01,731]; and site 7: July 20, 2015 [MEC-2015-448]).
was funded by Medistim. The principal investigators and authors had complete scientific freedom. This subanalysis received no funding. The study is registered at ClinicalTrials.gov (NCT02385344).
Overall Patient Population
Patients diagnosed with multivessel coronary artery disease and scheduled for isolated CABG were eligible to be included. Patients were excluded from enrollment if undergoing emergency surgery, when concomitant surgical procedures were planned (eg, valve repair or replacement, surgery for arrhythmias, etc), if the medical history included the presence of a muscle disorder (eg, myopathy, myalgia, myasthenia), or if the patient was known to be suffering from any psychological, developmental, or emotional disorder. The decision of performing the CABG operation with versus without the aid of cardiopulmonary bypass (ONCAB vs OPCAB) was left to the discretion of the operating surgeon.
It was highly recommended, but not mandatory, to assess each conduit used for CABG intraoperatively using TTFM. Only TTFM studies with an acoustic coupling index (ACI; as a correlate of the quality or reliability of the TTFM measurements) >30% were included in the analysis.
The following 4 TTFM parameters were defined as the primary outcome and were measured and recorded: mean graft flow (MGF; usually represented in mL/min and coupled with electrocardiogram), pulsatility index (PI; this is an absolute number that provides information on resistance and flow patterns with lower values representing lower resistance), diastolic fraction (DF; this is the percent of diastolic flow in the graft. Ideally, this should be more than 50%) and backflow (BF; this represents the percent of backward flow over the anastomosis during 1 cardiac cycle). Such parameters were measured after protamine administration for heparin reversal. When a graft was revised, the measurements included in the analysis were those measured after graft revision.
Inclusion and Exclusion Criteria
We considered only single grafts (ie, with only 1 distal anastomosis and no or 1 proximal anastomosis) with postprotamine TTFM performed with an ACI >30 (Figure 1). Sequential and Y/T grafts were therefore excluded from our analysis. We compared the median values of such parameters in ONCAB versus OPCAB procedures, considering all conduits (venous, arterial, and combined venous-arterial), completely arterial conduits, completely venous conduits, and specific conduit to target subsets: left internal mammary artery (LIMA) to left anterior descending (LAD), right internal mammary artery (RIMA) to LAD, RIMA to obtuse marginal (OM), radial artery (RA) to OM, RA to posterior descending artery, saphenous vein graft (SVG) to diagonal branch, SVG to OM, SVG to posterior descending artery, and SVG to right coronary artery.
Continuous data are reported as median (25th-75th percentile; ie, interquartile range), and categorical data as number (percentage). Comparisons were performed using the χ2, Fisher exact, and Wilcoxon rank sum tests as deemed appropriate (because normality was not established on the basis of Q-Q plots and the Shapiro–Wilk test), with the co-primary (ie, TTFM parameters) end points analyzed with P < .0125, taking into account multiple testing (Bonferroni correction). As a secondary analysis, propensity score matching (PSM; 1:1 ratio) was performed to balance the OPCAB and the ONCAB groups. The PSM was done using Greedy matching, and it was performed for all unbalanced variables (ie, age, body mass index, and New York Heart Association classification). The co-primary end points were analyzed with P < .0125, considering multiple testing (Bonferroni correction). We also analyzed the number of grafts not reaching specific parameter thresholds (MGF <20 mL/min, PI < 5, BF >3%, DF < 50%) and reviewed whether these grafts were revised. Analyses were performed using SAS 9.4 software (SAS Institute Inc).
Of 1016 patients enrolled in the REQUEST registry, 846 had at least 1 single graft for which TTFM was performed (after protamine administration) with an ACI >30% and were included in our study (809 grafts were excluded for sequential grafting or Y/T grafting, 158 had an ACI <30%, and 519 grafts had both exclusion criteria). Of these, 512 patients (60.6%) underwent ONCAB and 334 (39.4%) OPCAB, corresponding to 1050 ONCAB grafts (61.1%) and 669 OPCAB grafts (38.9%).
Baseline characteristics and postoperative in-hospital outcomes are reported in Table 1. Before PSM, patients in the ONCAB group were slightly older compared with the OPCAB patients (68 years vs 66 years, respectively; P = .006). Patients in the ONCAB group had a slightly lower rate of type 2 diabetes mellitus (28.3% vs 32.0%, respectively; P = .27). Other than age, the only other difference between groups was the body mass index, which was slightly lower for the ONCAB group than the OPCAB group (27.6 vs 28.3; P = .03). In-hospital morbidity and mortality rates were very low, with a numerically lower rate of stroke in the OPCAB group (1.8% for ONCAB vs 0.3% for OPCAB; P = .1) Use of PSM resulted in 2 well balanced groups of 312 patients each (Table 2).
Table 1Baseline characteristics and in-hospital outcomes of patient who underwent on- versus off-pump coronary artery bypass grafting
ONCAB (n = 512 patients)
OPCAB (n = 334 patients)
Body mass index
History of stroke
History of myocardial infarction
History of revascularization
In-hospital postoperative MACCE
Data are reported as mean (standard deviation) or %(n/N).
ONCAB, On-pump coronary artery bypass; OPCAB, off-pump coronary artery bypass; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; NYHA, New York Heart Association; MACCE, major adverse cardiac and cerebrovascular events; NA, not applicable.
Results of the comparison of ONCAB and OPCAB grafts (per graft analysis after PSM) are reported in Table 3 and Figure 2. Of note, 64% of LAD grafts in the ONCAB group were available for analysis and 75% of the LAD grafts were available in the OPCAB group. Most of the exclusions in this group of grafts were because of sequential grafting with a low ACI being the second most common reason (no major between group differences). Of the 406 single LIMA grafts in this analysis, 4 (0.98%) were free grafts anastomosed to the aorta. Of the 62 single RIMA grafts available for analysis, 11 (17%) were free grafts. MAP during measurements was higher in the OPCAB group. MGF was higher for ONCAB versus OPCAB (32 mL/min vs 28 mL/min, respectively, for all grafts; P < .001). This difference was more pronounced in venous than in arterial grafts (35 mL/min vs 31 mL/min [P = .005] and 30 mL/min vs 27 mL/min [P = .002], respectively). MGF was higher in ONCAB procedures for most conduit to target subsets taken together (apart from RIMA to LAD and SVG to RCA).
Table 3Comparison of transit time flowmetry parameters of on-versus off-pump coronary artery bypass procedures after propensity score matching
LIMA to LAD
RIMA to LAD
RIMA to OM
RA to OM
RA to PDA
SVG to Diag
SVG to OM
SVG to PDA
SVG to RCA
Data are reported as median (interquartile range). Units: MGF, mL/min; DF, %; and BF, %. Postprotamine TTFM measurements.
ONCAB, On-pump coronary artery bypass; OPCAB, off-pump coronary artery bypass; MGF, mean graft flow; PI, pulsatility index; DF, diastolic fraction; BF, backflow; LIMA, left internal mammary artery; LAD, left anterior descending artery; RIMA, right internal mammary artery; OM, obtuse marginal; RA, radial artery; SVG, saphenous vein graft; Diag, diagonal; PDA, posterior descending artery; RCA, right coronary artery.
PI was lower in the ONCAB group (2.1 vs 2.3, for all grafts; P < .001). This difference was more pronounced in venous grafts than in arterial grafts (1.9 vs 2.4 [P < .001] and 2.2 vs 2.3 [P = .369], respectively). DF was slightly lower in the ONCAB group than in the OPCAB group (65% vs 67.5%, respectively; P < .001). The DF measured separately for venous and arterial grafts showed the same trend. The BF was also lower in ONCAB than in OPCAB (0.6 vs 1.3, respectively, for all grafts; P < .001) with similar trends for venous and arterial grafts as MGF and PI (Figure 3). Regarding anastomotic revisions, there were 21 (3.3%) revisions in the OPCAB group and 14 (2.1%) in the ONCAB group (P = .198; Table 4). In the OPCAB group, most of these revisions were for a LIMA to LAD and in the ONCAB there was a more equal distribution (Table 4). Between group comparisons of grafts that did not meet parameter thresholds showed that almost 50% of grafts had at least 1 parameter that did not reach the accepted parameter threshold (Table 5). The only parameter that was different between ONCAB and OPCAB was BF for which it was much more common for OPCAB patients to not reach the threshold (32.9% OPCAB vs 23.9% ONCAB; P = .006). For the 2 most common threshold parameters (ie, MGF and PI), we also checked whether grafts not reaching the thresholds were more likely to undergo revision and found no difference for the 2 groups (Table 5).
Table 4Anastomotic revision rates and details according to group
OPCAB (n = 627)
ONCAB (n = 645)
OPCAB, Off-pump coronary artery bypass; ONCAB, on-pump coronary artery bypass; LIMA, left internal mammary artery; RIMA, right internal mammary artery; RA, radial artery; SVG, saphenous vein graft; LAD, left anterior descending artery; OM, obtuse marginal; RCA, right coronary artery; PDA, posterior descending artery.
In one of the largest multicenter cohorts existing thus far, ONCAB MGF was higher than OPCAB MGF and ONCAB PI was lower than OPCAB PI, despite consistently higher MAP values during measurement in the OPCAB patients. This finding was true for all grafts and for most coronary territories, but the difference was more pronounced in venous than in arterial grafts. The difference in MGF values ranged from no difference (RIMA to LAD and SVG to RCA) to 10 mL/min (RA to OM; P = .061) whereas the difference in PI ranged from no difference (RIMA to OM and RIMA to LAD) to 0.5 (SVG to OM; P = .002). These differences in MGF and PI for ONCAB and OPCAB could be an inherent characteristic of the procedures (ie, due to vasodilatation resulting from the use of cardiopulmonary bypass and the reactive hyperemia resulting from ischemic arrest) or a sign of the higher technical demands of OPCAB grafting. Regardless of the reason—this difference might have clinical implications, especially regarding MGF in venous grafts for which differences were substantial compared with the accepted cutoff value of 20 mL/min.
Previous reports have shown conflicting results regarding whether the differences in MGF and PI are inherent to the procedures themselves or a marker of the technical difficulty of OPCAB.
reported significantly lower graft flow values in the OPCAB group but with less myocardial damage, as reflected by lower postoperative cardiac enzyme levels in the OPCAB group (896 patients, 695 ONCAB and 201 OPCAB), with a total of 2247 grafts (1952/295, respectively). They attributed the higher flow rates and the higher levels of cardiac enzymes in the ONCAB group to myocardial hyperemia in response to metabolic acidosis caused by myocardial ischemia during crossclamp application. In contrast, Kjaergard and colleagues
reported no significant difference in graft flow values for the ONCAB and OPCAB groups after correction for flow per anastomosis; they attributed the lower total flow rates in the OPCAB group to fewer total grafts (120 ONCAB, 97 OPCAB). Hassanein and colleagues
reported lower OPCAB graft flow rates and higher PI values in all myocardial territories except for the LAD territory, which had flow rates and PI values similar to the ONCAB group (445 OPCAB patients paired with 445 ONCAB with 845 bypasses in each group). They concluded that this discrepancy between the OPCAB flow rates and PI of the LAD territory and the other territories might be the result of technical reasons related to accessibility of target vessels in the lateral and posterior territories. Balacumaraswami and colleagues
reported higher MGF and a higher flow-to-pressure ratio (because MGF is dependent on MAP) for all conduits in the ONCAB group despite a significantly lower MAP (80 OPCAB patients and 20 ONCAB; 203/63 grafts, respectively). They offered 2 explanations for this finding—the aforementioned increase in coronary blood flow as a result of ischemia in ONCAB and systemic vasodilatation as a result of a more pronounced inflammatory response in the ONCAB. Last, in a more recent report, Amin and colleagues
focused on grafts to the left system, reported higher flows in arterial grafts in ONCAB versus OPCAB (with higher MGF rates measured in the arterial and the venous grafts compared with the REQUEST database). They reported no difference in PI for ONCAB and OPCAB, both in arterial and venous grafts.
In a recent meta-analysis of intraoperative graft flow profiles ONCAB versus OPCAB MGF was compared as a secondary outcome.
was designed to prospectively evaluate the implementation of intraoperative graft quality assessment with TTFM and high-frequency ultrasound. It enrolled 1046 patients who underwent CABG, 30 of whom were excluded on the basis of predetermined criteria. Of the procedures, 39.6% (402/1016) were performed off-pump with a total of 1606 ONCAB grafts and 1069 OPCAB grafts. There was no difference in in-hospital mortality for the 2 groups. There was also no difference in in-hospital major cardiac and cerebrovascular events, strokes or transient ischemic attacks, myocardial infarctions, or repeat revascularizations. We retrospectively reviewed the REQUEST database to compare TTFM parameters for ONCAB versus OPCAB procedures. MGF was higher for ONCAB versus OPCAB (32 mL/min vs 28 mL/min, respectively, for all grafts; P < .001). This difference was more pronounced in venous than in arterial grafts (35 mL/min vs 31 mL/min [P = .005] and 30 mL/min vs 27 mL/min [P = .002], respectively). The PI was lower in the ONCAB versus the OPCAB group (2.1 vs 2.3, respectively; P < .001) with a more pronounced difference in the venous grafts.
Anastomotic revision rates were lower in this specific cohort (3.3% OPCAB, 2.1% ONCAB; Table 4) than in the REQUEST trial. This might stem from the fact that we used only single grafts in this analysis (in an attempt to reduce confounding) and thus less complex grafting required fewer revisions. There were more LIMA to LAD revisions in the OPCAB group, but the numbers were small, preventing comparison.
When interpreting TTFM values as threshold values (Table 5) we found that almost 50% of grafts had at least 1 parameter that did not meet parameter thresholds. Regarding revision rates for the most frequently used parameters (MGF and PI), we could not ascertain that surgeons have a different approach to cutoff values for OPCAB and ONCAB.
In our cohort, the increased MGF in ONCAB procedures did not correlate with better in-hospital clinical outcomes in the REQUEST trial. This finding is in accordance with previous studies that showed comparable postoperative angiographic patency for ONCAB and OPCAB, despite these reduced TTFM parameters.
It follows that the lower flow rates and higher PI values measured in OPCAB surgery could be intrinsic to the procedure. These differences probably result from the lack of ischemia (and subsequent hyperemia) in OPCAB.
If this hypothesis is true, then we must examine the clinical implications that these data might have. We need to consider for example, the higher immediate graft flow in ONCAB (especially when using venous grafts) when choosing the most appropriate surgical revascularization technique in an urgent scenario (ie, a patient in an acute myocardial infarction or in cardiogenic shock) versus an elective CABG. Furthermore, investigation is needed to correlate off- and on-pump parameters with graft patency and determine specific, clinically significant cutoff values for each type of procedure because lower MGF might still be satisfactory in the OPCAB patient. This is especially relevant when considering that a cutoff value of MGF >20 mL/min is considered adequate and the difference in flow for OPCAB and ONCAB reached 10 mL/min in some of the grafts in our study. By tracking this change in flow for ONCAB versus OPCAB we hope to improve intraoperative decision-making in the evaluation of graft quality using TTFM (Video Abstract).
The major limitation of this study stems from the lack of randomization of the patients in the REQUEST trial to ONCAB versus OPCAB. Furthermore, there was no equal distribution of OPCAB procedures performed in the various participating centers. As such, the differences in flow parameters in this study might have been the result of unidentified and unmeasured confounding variables for ONCAB and OPCAB patients not controlled for by PSM or the result of divergent surgical techniques of the different centers. Follow-up was limited to 30 days with no angiographic results, limiting our ability to draw clinical conclusions from our findings.
D. J. Thuijs, G. Di Giammarco, D. Wendt, T. M. Kieser, A. P. Kappetein, S. J. Head, J. D. Puskas, and D. P. Taggart reported traveling support/speaking fees from Medistim. A. P. Kappetein and S. J. Head reported Medtronic employment. D. P. Taggart reported Medistim research funding, speaking, traveling honoraria, and consultant. All other authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.