Abstract
Background: Studies on the relationship between the preoperative quantitative flow ratio (QFR) and parameters of intraoperative transit time flow measurement (TTFM) are extremely rare. In addition, the predictive value of QFR and TTFM parameters for early internal mammary artery (IMA) failure after coronary artery bypass grafting still needs to be validated.
Methods and Results: We retrospectively collected data from 510 patients who underwent in situ IMA grafting to the left anterior descending (LAD) artery at Fuwai Hospital. Spearman correlation coefficients between preoperative QFR of the LAD artery and intraoperative TTFM parameters of the IMA were −0.13 (P=0.004) for mean graft flow (Qm) and 0.14 (P=0.002) for the pulsatility index (PI). QFR and TTFM exhibited similar and good predictive value for early IMA failure (5.7% at 1 year), and they were better than percentage diameter stenosis (area under the curve 0.749 for QFR, 0.733 for Qm, 0.688 for PI, and 0.524 for percentage diameter stenosis). The optimal cut-off value of QFR was 0.765. Both univariate and multivariable regression analyses revealed that QFR >0.765, Qm ≤15 mL/min, and PI >3.0 independently contributed to early IMA failure.
Conclusions: There were statistically significant correlations between preoperative QFR of the LAD artery and intraoperative TTFM parameters (Qm, PI) of the IMA. Preoperative QFR and intraoperative Qm and PI exhibited excellent predictive value for early IMA failure.
The quantitative flow ratio (QFR) is a novel method for assessing the functional significance of coronary stenosis by using 3-dimensional vascular reconstruction technology and fluid dynamics algorithms in coronary angiography.1,2 In contrast to fractional flow reserve (FFR), QFR offers the advantages of circumventing the invasive impact of guidewires, requiring no administration of vasoactive drugs and facilitating real-time assessment within the catheterization laboratory.1,2 Previous studies, such as the FAVOR (Functional Diagnostic Accuracy of Quantitative Flow Ratio in Online Assessment of Coronary Stenosis) II China and Europe-Japan studies, showed a strong correlation and consistency between the QFR and FFR.3,4
Transit time flow measurement (TTFM), which relies on the time differential of ultrasound propagation in the bloodstream, is an instantaneous technique for measuring coronary blood flow.5,6 Due to its minimal invasiveness, short duration and high reproducibility, the TTFM has progressively emerged as an essential tool for swiftly evaluating graft quality in coronary artery bypass grafting (CABG) procedures.5 Of the TTFM parameters, mean graft flow (Qm) and the pulsatility index (PI) are the most frequently used. Both the 2014 and 2018 European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) guidelines on myocardial revascularization recommend routine incorporation of TTFM in CABG procedures (Class IIa, Level B).7,8
Recent research on the relationship between FFR and TTFM variables showed that as the severity of coronary stenosis increased (indicated by decreasing FFR), there were discernible variations in the corresponding TTFM indices.9 In 2021, Noda et al conducted a study that showed that preoperative FFR was significantly negatively correlated with Qm and significantly positively correlated with the PI.10 Currently, although QFR has been increasingly used in CABG, there is still a significant gap in studies regarding the relationship between QFR and TTFM parameters during CABG. Therefore, the aims of the present study were to: (1) investigate correlations between the preoperative QFR of the left anterior descending (LAD) artery and intraoperative TTFM parameters of the internal mammary artery (IMA); and (2) compare the predictive value of preoperative QFR and intraoperative TTFM parameters for early IMA failure after CABG.
Methods
This retrospective study was approved by the Ethics Committee of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 2021-1554). The requirement for informed consent to use clinical data was waived by the Ethics Committee of Fuwai Hospital due to the retrospective nature of the study.
Study Patients
Adult patients who underwent CABG at Fuwai Hospital, Beijing, between January 2016 and January 2020 were assessed for eligibility. To be eligible for inclusion in this study, patients had to have undergone coronary angiography at Fuwai Hospital within 6 months before surgery, completed the routine 1-year coronary computed tomography angiography (CCTA) follow-up at Fuwai Hospital, received an IMA graft to the LAD, and have complete TTFM data records (Qm and PI).
Patients with venous grafts on LAD arteries were excluded from the study. The coronary angiographic exclusion criteria were as follows: (1) total occlusion in the LAD or left main coronary artery (LMCA); (2) severe vessel overlap or tortuosity at stenotic segments; and (3) poor image quality during angiography that hindered accurate contour detection. The study flowchart is shown in Figure 1.
Coronary Angiography
Coronary angiography was conducted using standard percutaneous techniques (via the femoral or radial approach) with 5-Fr or 6-Fr diagnostic or guiding catheters. Angiographic images were captured at a rate of 15 frames per second using monoplane or biplane X-ray systems (including AXIOM-Artis [Siemens], Innova [GE], AlluraXper [Philips], and INTEGRIS Allura [Philips]). The contrast medium was administered manually with a stable injection or via a pump at a rate of approximately 4 mL/s. The evaluation of stenosis severity (percentage diameter stenosis [%DS]) was conducted visually by experienced operators who were not involved in subsequent data analysis. The %DS of the proximal, middle and distal segments of the LAD and LMCA were recorded separately; the maximum %DS was selected to represent the %DS of the whole vessel and use in subsequent data analysis.
Coronary Artery Bypass Surgery
All patients underwent general anesthesia and median sternotomy. The IMA was used for revascularization of the LAD for all patients included in this study. The IMA was harvested with a pedicle. The procedures for harvesting the left IMA (LIMA) or right IMA (RIMA) at Fuwai Hospital are as follows. First, a median sternotomy was performed. The LIMA was carefully harvested; it was dissected upwards to the subclavian vein and down to the distal branches (musculophrenic and superior epigastric arteries). Importantly, the LIMA must be separated from the first intercostal artery to prevent steal syndrome. Approximately 3–5 min before the distal end of the LIMA was cut, systemic heparin was administered. Papaverine saline solution was injected into the fascial plane surrounding the LIMA, and gauze moistened with papaverine solution was gently wrapped around the vessel to keep it until it was used later. The harvesting technique for the RIMA was similar to that for the LIMA.
At Fuwai Hospital, the indications for off-pump CABG include advanced age, severe pulmonary disease, renal insufficiency, severe atherosclerosis of the aorta, and an inability to tolerate hemodynamic changes during cardiopulmonary bypass (e.g., patients with compromised cardiac function or hemodynamic instability). In addition, the surgeons also decided whether to perform off-pump or on-pump CABG based on their clinical expertise and judgment. All surgeons performing the procedures in this study were proficient in CABG and had completed more than 100 CABG surgeries. Concomitant procedures were performed simultaneously with CABG. In these cases, neither Y-grafting nor sequential grafting techniques were used in IMA-LAD.
TTFM
Intraoperative graft flow measurements are routinely performed at Fuwai Hospital according to the ESC and EACTS guidelines on myocardial revascularization.7,8 TTFM was completed during CABG. A 2- or 3-mm flow probe (Medistim, Oslo, Norway) was placed around the graft for the intraoperative measurement of TTFM parameters. TTFM was implemented twice during CABG: once immediately after graft anastomosis during off-pump CABG and on-pump beating-heart CABG or immediately after aortic declamping during on-pump cardioplegia arrest CABG, to assess the necessity of graft revision; and then again for both off-pump CABG and on-pump CABG patients, when the hemodynamic status is stable before chest closure (and mean blood pressure is between 70 and 90 mmHg and heart rate ranges from 70 to 100 beats/min). The TTFM data obtained during the patient’s stable hemodynamic state were used in this study. The analysis of blood flow data yielded 2 key parameters: Qm (mL/min) and PI (calculated as [maximum flow volume−minimum flow volume] / Qm).
QFR Measurement
The QFR was retrospectively measured based on preoperative coronary angiograms. The QFR analysis was performed using AngioPlus Core software (developed by Pulse Medical Imaging Technology, Shanghai, China). This analysis was performed by 2 experienced analysts (Z. Hou and L.S.) who were unaware of the study outcomes.
The process for calculating QFR can be summarized as follows: first, an angiographic run that provided clear visualization of the stenosis in the LAD coronary artery was selected; second, the lumen contour of the LAD artery was automatically delineated (in cases of suboptimal angiographic image quality, manual corrections were allowed); and third, the QFR virtual pullback was reconstructed and the report generated. For patients with LMCA stenosis ≥50%, the view that showed lesions of the LAD and LMCA simultaneously was used, and the delineated lumen contour covered the LAD and LMCA simultaneously.
Representative examples of the QFR measurement process are provided in Figure 2.
Graft Quality Assessment
The quality of the graft was evaluated through regular CCTA examination (as recommended at Fuwai Hospital) conducted at 1 year (with a window of ±3 months) and graded based on modified FitzGibbon criteria.11 There were 4 grading levels: Grade 0, complete graft occlusion; Grade 1, significant stenosis (lumen stenosis ≥50% in any segment of the graft); Grade 2, moderate stenosis (lumen stenosis <50% in any segment of the graft); and Grade 3, a fully patent graft. Graft failure was determined if the patient received a Grade 0 assessment.
Statistical Analysis
The normality of distribution of continuous variables was tested using the Shapiro-Wilk test. Continuous variables are reported as either the mean±SD (normal distribution) or as the median with interquartile range (IQR). Categorical variables are presented as counts and percentages. We computed Spearman correlation coefficients to evaluate associations between intraoperative TTFM variables of the IMA and the preoperative QFR of the LAD. We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate the ability of the QFR, PI, Qm, and %DS to predict early IMA failure. Continuous variables were compared using Student’s t-test for normally distributed continuous variables or the Mann-Whitney U test for non-normally distributed variables. Categorical variables were compared using the Chi-squared test or Fisher’s exact test. Univariate analyses were performed through univariate logistic regression analysis without multiple testing correction. In the multivariable logistic regression analysis, variables with P<0.1 in the univariate analysis and variables that influenced graft patency according to clinical experience or reported in the literature were included.
We conducted statistical analyses using R version 4.1.2 (R Foundation for Statistical Computing). Statistical significance was set at 2-sided P<0.05. The primary authors and corresponding authors have complete access to the data, and the corresponding authors assume full responsibility for the accuracy and integrity of the data.
Results
Baseline Characteristics
Eventually, 510 patients were included in the final analysis (Figure 1). Table 1 summarizes the characteristics of all patients included; 76.9% were male. The median age was 61.8 years (IQR 55.6–66.2 years), and 7.5% of patients had a left ventricular ejection fraction (LVEF) <50%. More than half the patients underwent surgery with the assistance of cardiopulmonary bypass; 97.4% underwent isolated CABG procedures and 1.2% underwent concomitant valve surgery. Regarding graft vessel selection, the LIMA was used in 93.1% of patients, whereas the RIMA was only chosen for 6.9% of patients. All patients were routinely transferred to the intensive care unit for postoperative monitoring. Postoperatively, 1.8% of patients experienced complications (including bleeding, heart failure, and reoperation). The median length of hospital stay was 15.6 days (IQR 13.4–19.6 days). No patients experienced perioperative myocardial infarction (identified by electrocardiographic changes and serum creatine kinase MB isozyme levels), and no patients died in the hospital or within 30 days after CABG.
Table 1.
Baseline Characteristics of All Patients Included (n=510)
| Male sex |
392 (76.9) |
| Age (years) |
61.8 [55.6–66.2] |
| BMI (kg/m2) |
25.9 [23.7–27.7] |
| Smoker |
297 (58.2) |
| Hypertension |
356 (69.8) |
| Hypercholesterolemia |
422 (82.7) |
| Diabetes |
195 (38.2) |
| Prior PCI |
30 (5.9) |
| Prior MI |
119 (23.3) |
| Peripheral vascular disease |
31 (6.1) |
| LVEF <50% |
38 (7.5) |
| NYHA functional class |
| I |
46 (9.0) |
| II |
262 (51.4) |
| III |
198 (38.8) |
| IV |
4 (0.8) |
| QFR |
0.59 [0.41–0.74] |
| Angiographic vessel disease |
| 1 vessel disease |
6 (1.2) |
| 2 vessel disease |
58 (11.4) |
| 3 vessel disease |
301 (59.0) |
| LMCA+1 vessel disease |
3 (0.6) |
| LMCA+2 vessel disease |
23 (4.5) |
| LMCA+3 vessel disease |
119 (23.3) |
| %DS |
90.0 [80.0–90.0] |
| On-pump |
260 (51.0) |
| Isolated CABG |
497 (97.4) |
| Concomitant surgery |
| Valvular surgery |
6 (1.2) |
| OtherA |
7 (1.4) |
| Graft material |
| LIMA |
475 (93.1) |
| RIMA |
35 (6.9) |
| PI |
2.0 [1.7–2.6] |
| Qm (mL/min) |
25.0 [18.0–36.0] |
| In-hospital complicationsB |
9 (1.8) |
| Hospital stays (days) |
15.6 (13.4–19.6) |
| In-hospital or 30-day death |
0 (0) |
Data are presented as n (%) or median [interquartile range]. AOther concomitant surgeries included left atrial appendectomy, ventricular aneurysmectomy, carotid endarterectomy, and arteriovenous fistula surgery. BIn-hospital complications included bleeding, heart failure, and reoperation. BMI, body mass index; CABG, coronary artery bypass grafting; %DS, percentage diameter stenosis; LIMA, left internal mammary artery; LMCA, left main coronary artery; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; PI, pulsatility index; QFR, quantitative flow ratio; Qm, mean graft flow; RIMA, right internal mammary artery.
Correlations Between QFR and TTFM Parameters
A significant negative correlation was identified between preoperative QFR and intraoperative Qm (r=−0.13; P=0.004; Figure 3A). Conversely, a significant positive correlation was observed between preoperative QFR and intraoperative PI (r=0.14; P=0.002; Figure 3B). We further conducted subgroup analyses of patients with different graft vessels. As shown in Supplementary Figure 1A, there was a significant negative correlation between preoperative QFR and intraoperative Qm regardless of whether the graft vessel was the LIMA (r=−0.11, P=0.018) or RIMA (r=−0.34, P=0.049). Conversely, there was a significant positive correlation between QFR and PI for both the LIMA (r=0.12; P=0.007) and RIMA (r=0.58; P<0.001) graft vessels (Supplementary Figure 1B).
ROC Analysis of QFR and TTFM for Predicting IMA Failure
Of the 510 individuals who completed the follow-up, and 29 (5.7%) patients experienced IMA failure at 1 year (Supplementary Table). With regard to clinical outcomes at follow-up, the rate of recurrent angina was 1.6% (8/510) and the rate of repeat revascularization (percutaneous coronary intervention) was 0.6% (3/510) at 1 year. As shown in Figure 4A, the QFR and TTFM parameters (PI and Qm) exhibited similar predictive capabilities for IMA failure at 1 year (AUC 0.749, 0.733, and 0.688 for QFR, Qm, and PI, respectively), surpassing the predictive capability of %DS (AUC 0.524).
Identification of Risk Factors for Early IMA Failure
Based on the occurrence of graft failure, patients were stratified into 2 groups: an IMA patency group (n=481) and an IMA failure group (n=29). The results of comparative analysis are presented in Table 2. There were significant differences between the IMA patency and failure groups in terms of the preoperative QFR, LMCA lesion, PI, and Qm. However, no significant differences were observed between the 2 groups in %DS, graft material, hospital complications, or hospital stay.
Table 2.
Characteristics of Patients According to Internal Mammary Artery Patency or Failure
| |
Patency
(n=481) |
Failure
(n=29) |
P value |
| Male sex |
369 (76.7) |
23 (79.3) |
0.924 |
| Age (years) |
61.9 [55.6–66.2] |
61.5 [56.6–66.1] |
0.784 |
| BMI (kg/m2) |
25.9 [23.5–27.7] |
26.1 [25.0–27.3] |
0.464 |
| Smoker |
278 (57.8) |
19 (65.5) |
0.532 |
| Hypertension |
337 (70.1) |
19 (65.5) |
0.757 |
| Hypercholesterolemia |
396 (82.3) |
26 (89.7) |
0.447 |
| Diabetes |
183 (38.0) |
12 (41.4) |
0.871 |
| Prior PCI |
28 (5.8) |
2 (6.9) |
0.685 |
| Prior MI |
112 (23.3) |
7 (24.1) |
>0.99 |
| Peripheral vascular disease |
28 (5.8) |
3 (10.3) |
0.409 |
| LVEF <50% |
35 (7.3) |
3 (10.3) |
0.468 |
| NYHA Class III or IV |
189 (39.3) |
13 (44.8) |
0.563 |
| QFR |
0.58 [0.40–0.72] |
0.79 [0.67–0.87] |
<0.001 |
| Including LMCA disease |
142 (29.5) |
3 (10.3) |
0.032 |
| %DS |
90.0 [80.0–90.0] |
80.0 [80.0–90.0] |
0.636 |
| On-pump |
246 (51.1) |
14 (48.3) |
0.913 |
| Isolated CABG |
468 (97.3) |
29 (100.0) |
>0.99 |
| Concomitant surgery |
|
|
>0.99 |
| Valvular surgery |
6 (1.2) |
0 |
|
| OtherA |
7 (1.5) |
0 |
|
| Graft material |
|
|
0.439 |
| LIMA |
449 (93.3) |
26 (89.7) |
|
| RIMA |
32 (6.7) |
3 (10.3) |
|
| PI |
2.0 [1.7–2.5] |
2.5 [2.1–3.4] |
0.001 |
| Qm (mL/min) |
26.0 [19.0–37.0] |
18.0 [13.0–22.0] |
<0.001 |
| In-hospital complicationsB |
7 (1.5) |
2 (6.9) |
0.088 |
| Hospital stays (days) |
15.6 [13.4–19.6] |
17.6 [13.4–21.4] |
0.312 |
| PI >3.0 |
49 (10.2) |
9 (31.0) |
0.003 |
| Qm ≤15 mL/min |
64 (13.3) |
13 (44.8) |
<0.001 |
Unless indicated otherwise, data are presented as n (%) or the median [interquartile range]. AOther concomitant surgeries included left atrial appendectomy, ventricular aneurysmectomy, carotid endarterectomy, and arteriovenous fistula surgery. BIn-hospital complications included bleeding, heart failure, and reoperation. Abbreviations as in Table 1.
The optimal cut-off value for predicting early IMA failure was determined through receiver operating characteristic (ROC) analysis. The optimal cut-off value for QFR was 0.765 (sensitivity 58.6%, specificity 83.0%), with an AUC of 0.749 (Figure 4B). The optimal cut-off values for Qm and PI are shown in Supplementary Figure 2. In the IMA failure and patency groups, 82 (17.0%) and 17 (58.6%) patients, respectively, had a QFR >0.765 (P<0.001). According to previous studies, the most commonly used cut-off values for Qm and PI are 15 mL/min and 3.0, respectively.12–14 In the present study, the IMA was considered good if its Qm was >15 mL/min and PI was ≤3.0. Compared with the graft patency group, a higher proportion of patients in the graft failure group had a Qm ≤15 mL/min (44.8% vs. 13.3%; P<0.001) and a PI >3.0 (31.0% vs. 10.2%; P=0.003; Table 2).
According to univariate logistic analysis, factors linked to an elevated risk of IMA failure at 1 year included QFR >0.765 (odds ratio [OR] 6.89; 95% confidence interval [CI] 3.17–14.98; P<0.001), PI >3.0 (OR 3.97; 95% CI 1.71–9.19; P=0.001), LMCA disease (OR 0.28; 95% CI 0.08–0.92; P=0.037) and Qm ≤15 mL/min (OR 5.29; 95% CI 2.43–11.52; P<0.001; Table 3). Covariates adjusted for clinical outcomes included traditional cardiovascular risk factors (sex, age, body mass index, smoking status, hypertension, hypercholesterolemia, diabetes, prior percutaneous coronary intervention, prior myocardial infarction, peripheral vascular disease, LVEF <50%, New York Heart Association Class III or IV), surgery and hospital-related risk factors (on-pump surgery, concomitant surgery, graft material, hospital complications, hospital stays, PI >3.0, Qm ≤15 mL/min), variables with P<0.1 in univariate analysis (including LMCA disease, hospital complications) and QFR >0.765. According to multivariable logistic regression, QFR >0.765 (OR 8.61; 95% CI 3.45–21.47; P<0.001), PI >3.0 (OR 2.96; 95% CI 1.09–8.04; P=0.033), and Qm ≤15 mL/min (OR 5.80; 95% CI 2.24–15.03; P<0.001) remained associated with an increased risk of early IMA failure (Table 3).
Table 3.
Univariate and Multivariable Logistic Regression Analysis of Early Internal Mammary Artery Failure
| |
Univariate |
Multivariable |
| OR (95% CI) |
P value |
OR (95% CI) |
P value |
| Male sex |
1.16 (0.46–2.93) |
0.748 |
1.30 (0.34–5.03) |
0.702 |
| Age (years) |
1.00 (0.96–1.05) |
0.920 |
1.01 (0.95–1.07) |
0.760 |
| BMI (kg/m2) |
1.03 (0.92–1.15) |
0.622 |
1.03 (0.91–1.17) |
0.671 |
| Smoker |
1.39 (0.63–3.05) |
0.415 |
1.38 (0.47–4.04) |
0.555 |
| Hypertension |
0.81 (0.37–1.79) |
0.605 |
0.80 (0.31–2.06) |
0.644 |
| Hypercholesterolemia |
1.86 (0.55–6.29) |
0.318 |
1.19 (0.28–5.01) |
0.814 |
| Diabetes |
1.15 (0.54–2.46) |
0.720 |
0.99 (0.39–2.53) |
0.992 |
| Prior PCI |
1.20 (0.27–5.30) |
0.811 |
0.46 (0.06–3.77) |
0.470 |
| Prior MI |
1.05 (0.44–2.52) |
0.916 |
1.17 (0.34–4.05) |
0.807 |
| Peripheral vascular disease |
1.87 (0.53–6.55) |
0.329 |
2.51 (0.58–10.92) |
0.220 |
| LVEF <50% |
1.47 (0.42–5.10) |
0.543 |
2.45 (0.50–11.93) |
0.268 |
| NYHA Class III or IV |
1.26 (0.59–2.67) |
0.555 |
2.09 (0.83–5.22) |
0.116 |
| Including LMCA disease |
0.28 (0.08–0.92) |
0.037 |
0.30 (0.08–1.17) |
0.083 |
| %DS |
0.99 (0.95–1.04) |
0.845 |
|
|
| On-pump |
0.89 (0.42–1.89) |
0.764 |
0.92 (0.37–2.28) |
0.858 |
| Concomitant surgeryA |
0 |
0.989 |
0 |
0.988 |
| Graft material (RIMA vs. LIMA) |
1.62 (0.46–5.64) |
0.449 |
3.09 (0.54–17.58) |
0.204 |
| In-hospital complicationsB |
5.02 (0.99–25.31) |
0.051 |
6.22 (0.74–52.02) |
0.092 |
| Hospital stays |
1.00 (0.99–1.01) |
0.991 |
0.99 (0.98–1.01) |
0.967 |
| QFR >0.765 |
6.89 (3.17–14.98) |
<0.001 |
8.61 (3.45–21.47) |
<0.001 |
| PI >3.0 |
3.97 (1.71–9.19) |
0.001 |
2.96 (1.09–8.04) |
0.033 |
| Qm ≤15 mL/min |
5.29 (2.43–11.52) |
<0.001 |
5.80 (2.24–15.03) |
<0.001 |
AConcomitant surgery included valvular surgery, left atrial appendectomy, ventricular aneurysmectomy, carotid endarterectomy, and arteriovenous fistula surgery. BIn-hospital complications included bleeding, heart failure, and reoperation. CI, confidence interval; OR, odds ratio. Other abbreviations as in Table 1.
Discussion
This study has 2 key findings. First, intraoperative TTFM parameters (Qm and PI) of the LIMA and RIMA were strongly affected by the preoperative QFR. Second, the preoperative QFR and intraoperative TTFM exhibited similar and good predictive value for early IMA failure. In addition, elevated QFR (QFR >0.765), PI >3.0, and Qm ≤15 mL/min were found to be independent risk factors for early IMA failure.
TTFM is valuable for detecting the hemodynamics of CABG grafts and the physiology of the coronary circulation.5 In addition, TTFM parameters (specifically Qm) are modified in response to variations in dynamic characteristics, such as systolic blood pressure, heart rate, coronary resistance, graft mass, and anastomosis quality.15 In the present study, our primary focus was coronary artery resistance, and we used the QFR to assess the physiological stenosis of coronary arteries.
In a previous study conducted by Honda et al, patients were categorized into 3 groups based on FFR, and the TTFM parameters of the left internal thoracic artery (LITA)-LAD were compared among these groups.9 The results showed that patients with an FFR ≥0.75 had significantly lower Qm and greater PI than those with an FFR <0.70 or 0.70–0.75.9 Noda et al further elucidated the relationship between preoperative FFR and TTFM parameters of the LITA-LAD and reported a negative correlation between FFR and Qm, but a positive correlation between FFR and PI.10 Recently, a study led by Yoshiyuki Takami revealed that the Spearman correlation coefficients between the FFR of the LAD artery and the TTFM parameters (Qm and PI) of the LITA were −0.35 (P=0.039) and 0.33 (P=0.008), respectively.16 Our results also showed that a significant negative correlation between preoperative QFR and intraoperative Qm (r=−0.13; P=0.004), along with a significant positive correlation between preoperative QFR and intraoperative PI (r=0.14; P=0.002). A high QFR indicates that there is increased residual blood flow in the coronary arteries. The presence of competitive blood flow can disrupt IMA blood flow, resulting in reduced IMA flow and elevated resistance (evidenced by an increased PI).5
Chen et al explored the association between QFR and TTFM parameters in 2022.17 That study included 89 patients, 77 of whom underwent LIMA-LAD and 12 patients who received a saphenous vein graft (SVG).17 The correlation coefficients between preoperative QFR and the TTFM parameters (Qm and PI) in patients who underwent LIMA-LAD were −0.226 (P=0.036) and 0.265 (P=0.012), respectively.17 In contrast to that study,17 the present study included a comprehensive cohort of 510 patients who underwent IMA-LAD, with 93.1% receiving a LIMA graft and 6.9% receiving a RIMA graft. Notably, our sample size was approximately 6-fold larger than that of Chen et al.17 Furthermore, we conducted subgroup analyses based on different graft vessels and found that the preoperative QFR remained significantly correlated with TTFM parameters regardless of whether the graft vessel was the LIMA or the RIMA. In addition, compared with LIMA-LAD, the correlations between QFR and TTFM parameters were stronger for the RIMA graft. However, because only 6.9% of patients in the present study underwent RIMA-LAD, these results should be interpreted with caution.
Most previous studies focused on evaluating whether TTFM parameters were predictors of graft failure in the CABG perioperative period.12,18 Nevertheless, no agreement has yet been reached on the threshold for TTFM. In the present study, the primary focus was to assess the quality of IMA-LAD. Therefore, IMA-LAD was considered good when its Qm was >15 mL/min and PI was ≤3.0.12–14
In the present study, the rate of IMA failure at 1 year was 5.7%, which is consistent with previous studies.6,19,20 Lehnert et al reported that intraoperative graft flow had good discriminative ability for assessing IMA failure at 1 year (AUC 69.5%).21 Sugimoto et al conducted a post hoc analysis of the PRIDEMETAL (Prospective Multicenter Registry of Hybrid Coronary Artery Revascularization Combined With Non-Saphenous Vein Graft Surgical Bypass and Percutaneous Coronary Intervention Using Everolimus-Eluting Metallic Stents) registry and found that QFR was highly discriminative (AUC 0.89) in predicting arterial graft function 1 year after surgery.22 However, studies comparing the predictive value of QFR and intraoperative TTFM for early IMA failure are scarce. To our knowledge, the present study is the largest to date comparing QFR, Qm, and PI for predicting IMA failure at 1 year. Our study showed that the preoperative QFR and intraoperative TTFM parameters (Qm and PI) exhibited comparable and good predictive value for IMA failure at 1 year and were better than %DS.
Univariate and multivariable regression analyses revealed that QFR >0.765, Qm ≤15 mL/min, and PI >3.0 were found to be independent risk factors for early IMA failure. The effectiveness of CABG surgery relies on the graft flow dominating the pre-existing coronary blood flow.23 For a graft to be effective, the flow through the graft must surpass that through the native coronary artery. When the graft is implanted to the target coronary artery with non-significant stenosis, competitive flow between the 2 conduits weakens the function of the graft and accelerates its early failure.24 In addition, when the graft flow is competitive, the corresponding PI increases because the minimum flow is negative.5
Clinical Application
The following potential clinical applications were identified because the intraoperative TTFM parameters (Qm and PI) of the LIMA and RIMA were strongly affected by preoperative QFR, and the QFR and TTFM parameters exhibited similar and excellent predictive value for early IMA failure. First, when assessing the quality of the anastomosis in CABG surgery using the intraoperative TTFM, it is imperative to consider the statistically significant correlations between preoperative QFR and the TTFM parameters. This consideration is crucial for preventing unintended re-anastomosis or revision of grafts attributable to unfavorable TTFM parameters. Second, the QFR measurement should be incorporated into the preoperative preparation workup of patients who undergo CABG. In addition, a QFR >0.765 was a risk factor for early IMA graft failure. This means that patients who are at high risk of IMA problems (as determined by a preoperative QFR >0.765) need to be monitored more closely.
Study Limitations
This study has several limitations. First, this was a retrospective study, and only patients who completed follow-up at Fuwai Hospital were included, which may introduce a risk of selection bias. Second, QFR analysis was not possible for some patients due to technical reasons, and some patients lacked complete TTFM data records. Whether data from these excluded participants would have changed the associations between preoperative QFR and intraoperative TTFM (Qm and PI) is unknown. Third, patients who undergo CABG often have multiple coronary artery lesions requiring multiple revascularizations. In the present study, we limited our focus to IMA-LAD in situ grafts, and the effect of other grafts on the IMA was ignored. Fourth, although this study demonstrated significant correlations between QFR and TTFM parameters (Qm and PI), further confirmation through prospective randomized controlled studies is needed.
Conclusions
There were significant correlations between preoperative QFR and intraoperative TTFM parameters (Qm and PI). As QFR increased, Qm decreased gradually and PI increased gradually. Preoperative QFR and intraoperative Qm and PI all demonstrated excellent predictive value for early IMA failure. The preoperative application of QFR to assess the severity of LAD stenosis was beneficial for avoiding excessive IMA re-anastomosis or revision during CABG surgery and improving the status of the IMA after CABG. Therefore, the QFR should be used more often during CABG surgery, and the optimal cut-off value is 0.765. Patients who are at high risk of IMA problems (as indicated by a preoperative QFR >0.765) need to be monitored more closely.
Sources of Funding
This study was supported by grants from the National Natural Science Foundation of China (Grant no. 82172099), Beijing Natural Science Foundation (Grant no. 7212082), Chinese Academy of Medical Sciences Research Fund for Clinical and Translational Medicine (Grant no. 2020-I2M-C&T-B-058) and Beijing Nova Program (Grant no. Z201100006820003).
Disclosures
The authors have no conflicts of interest to disclose.
IRB Information
This retrospective study was approved by the Ethics Committee of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 2021-1554).
Data Availability
The deidentified participant data will not be shared.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-24-0078
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