Between March 17, 2009, and January 19, 2021, 1024 patients had FFR-guided DES implantation at our center. Of those, 534 did not have all treated vessels assessed by post-PCI FFR measurement. After excluding those after heart transplantation and graft PCI, 434 patients and 500 arteries were included in our analysis. The flowchart of patients is shown in Fig. 1.

The median age of the patient population was 65 years (IQR: 57–71), 69% were male, 49% had diabetes mellitus; of those, 27% were treated with insulin. Forty-four percent of the patient population had previous PCI and 2% had coronary artery bypass surgery. The characteristics of the patients are summarized in Table 1.

Of the 434 patients, 46 had 2 and 10 had 3 vessels included in our analysis. Of the 500 vessels, 333 (67%) were left anterior descending (LAD), 67 (13%) left circumflex (LCx), and 100 (20%) right coronary arteries (RCA). In 77 cases, the indication of PCI was ACS, in 62, the treated lesion was in-stent restenosis.

The distribution of pre-PCI FFR values is shown in Supplemental Fig. 1. Median pre-PCI FFR was 0.72 (IQR: 0.65–0.77), and no difference was found between LAD and non-LAD vessels (0.72 (IQR: 0.66–0.76) and 0.72 (IQR: 0.63–0.77]), p = 0.3011, respectively).

The number of implanted stents was 1.40 per vessel: 1 in 326 vessels (65.2%), 2 in 147 vessels (29.4%), and 3 in 27 vessels (5.4%).

The distribution of post-PCI FFR values is shown in Fig. 2. Median post-PCI FFR was 0.87 (IQR: 0.84–0.91). A post-PCI FFR of ≤ 0.80 was found in 21 arteries (4%), whereas a post-PCI FFR of > 0.95 was found in 44 arteries (9%). LAD vessels had lower post-PCI FFR value than non-LAD vessels (0.85 (IQR: 0.83–0.89) vs. 0.92 (IQR: 0.88–0.94), p < 0.001).

The distribution of post-PCI FFR values

The distribution of the difference between post and pre-PCI FFR values (ΔFFR) is shown in Supplemental Fig. 2. LAD vessels had lower ΔFFR than non-LAD vessels (0.14 (IQR: 0.10–0.21) vs 0.19 (IQR: 0.15–0.29), p < 0.001).

By multivariable regression analysis, LAD location (p < 0.001), male gender (p < 0.001), smaller stent diameter (p = 0.006), and lower pre-PCI FFR (p = 0.003) proved to be significant predictors of lower post-PCI FFR. Of note, post-PCI FFR measured in non-culprit vessels in ACS and in CCS did not differ significantly, neither had the in-stent restenosis vs. de novo lesion category or diabetes mellitus any significant influence on post-PCI FFR. This is shown in Fig. 3.

Predictors of post-PCI FFR

After a median follow-up of 37 months (IQR: 20–61), survival status is known in 433 of 434 patients (99.8%), whereas follow-up is complete for MI and TVR in 423 (97.5 %). During this period, 27 patients suffered CD, 20 had MI, and 52 TVR occurred. Of the 52 TVR, 10 were performed because of acute myocardial infarction, and 13 were FFR-guided (i.e., the FFR was ≤ 0.80 before TVR was performed). In 4 cases, the lesion was subtotally occlusive which the operator felt to be functionally significant, whereas in 25 cases the revascularization was purely angio-guided. In the latter group, FFR measurement could have resulted in the deferral of TVR. In all, 73 patients suffered TVF (17%), whereas 39 had MI or CD during follow-up (9%).

On a vessel-level, post-PCI FFR (p < 0.001), stent length (p < 0.001), and diabetes mellitus (p = 0.026) were found to be significant predictors of TVF (Fig. 4). The frequency of TVF in vessels with post-PCI FFR strata of ≤ 0.80, 0.81–0.85, 0.86–0.90, 0.91–0.95, and > 0.95 were 47.6%, 21.4%, 13.3%, 12.6%, and 2.3%, respectively. The relationship between TVF and post-PCI FFR as a continuous variable is shown in Fig. 5.

Significant predictors of TVF

Relationship between TVF and post-PCI FFR

By univariate ROC analysis, a post-PCI FFR of 0.83 was found to be the best cut-off to predict TVF according to the Youden-index with a sensitivity of 45%, specificity of 86%, and an area under the curve (AUC) of 0.70.

Given that the median post-PCI FFR values in the LAD were 0.07 units lower than in non-LAD vessels, we also studied these two territories separately. Two-thirds of the studied vessels were LAD, in these, the best post-PCI FFR, by univariate ROC analysis, was also 0.83 according to the Youden-index (sensitivity 60%, specificity 82%, AUC 0.75), whereas in the non-LAD vessels, accounting for one-third of the cases, the best post-PCI FFR to predict TVF was 0.91 according to the Youden-index (sensitivity 65%, specificity 61%, AUC 0.59).

The secondary endpoint of our study was the composite of CD and MI. Its independent predictors were post-PCI FFR (p < 0.001), stent length (p < 0.001), non-LAD location (p = 0.0026), and diabetes mellitus (p = 0.015), see Supplemental Fig. 3. The relationship between CD and/or MI and post-PCI FFR as a continuous variable is shown in Supplemental Fig. 4.

By univariate ROC analysis, a post-PCI FFR of 0.83 was found to be the best cut-off to predict the composite of CD and MI according to the Youden-index with a sensitivity of 54%, specificity of 86%, and an AUC of 0.75. In LAD vessels, the best cut-off to predict CD and/or MI according to the Youden-index was also 0.83 with a sensitivity of 72%, specificity of 82%, and an AUC of 0.84. In non-LAD vessels, the best cut-off to predict CD and/or MI according to the Youden-index was 0.91, with a sensitivity of 70%, specificity of 61%, AUC 0.60.

On a patient level, post-PCI FFR (p < 0.001) and stent length (p = 0.00384) were found to be independent predictors of TVF. The frequency of TVF in patients with the single lowest post-PCI FFR strata of ≤ 0.80, 0.81–0.85, 0.86–0.90, 0.91–0.95, and > 0.95 were 47.6%, 22.2%, 11.7%, 12.5%, and 2.9%, respectively. The relationship between TVF and the single lowest post-PCI FFR as a continuous variable is shown in Supplemental Fig. 5. Note that this figure uses the whole follow-up for each patient, i.e., it neglects the inter-patient differences in follow-up time.

By univariate ROC analysis, a single lowest post-PCI FFR of 0.83 was found to be the best cut-off to predict TVF according to the Youden-index with a sensitivity of 51%, specificity of 85% and an AUC of 0.73.

The independent predictors of the composite of CD and MI on a patient level were post-PCI FFR (p < 0.001), stent length (p < 0.001), and diabetes mellitus (p = 0.03377). By univariate ROC analysis, a single lowest post-PCI FFR of 0.83 was found to be the best cut-off according to the Youden-index to predict CD and/or MI with a sensitivity of 62%, specificity of 85% and an AUC of 0.81 on a patient-level.