Outcomes from Quantitative Flow Ratio-Guided Complete Revascularization and Angiography-Guided Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction

Introduction

Quantitative Flow Ratio (QFR) is a diagnostic tool used in the field of interventional cardiology to assess the severity of coronary artery stenosis. It is a noninvasive method that uses angiographic images to calculate the pressure drop across a coronary artery lesion and estimate the fractional flow reserve, without the need for a pressure wire or hyperemic agent [1].

QFR can potentially shorten stenting procedures, because interventional cardiologists can plan the intervention more effectively, knowing which lesions are physiologically significant and require treatment. The FAVOR III Europe trial suggested that the current QFR method can offer diagnostic clinical value that might be positioned between angiography and fractional flow reserve [2].

Traditional assessment methods, like fractional flow reserve, require the insertion of a pressure wire and administration of hyperemic agents, which extends fluoroscopic time [3]. QFR can provide similar diagnostic information without these steps [4]. With QFR providing detailed physiological data upfront, interventional cardiologists can plan stent placement more accurately and avoid unnecessary prolonged fluoroscopic imaging due to indecision or multiple adjustments during the procedure [5]. QFR has the potential to reduce the use of radiographic contrast agents during percutaneous coronary intervention (PCI) procedures [3]. The use of QFR can potentially lead to fewer stents being placed during PCI. In some cases, angiographic imaging alone may suggest that a lesion is severe and needs stenting, while in reality, it may not significantly impair blood flow [8]. QFR provides additional functional information that can prevent over-treatment by showing that some lesions do not require stenting [9]. Avoiding unnecessary stents can reduce the risk of stent-related complications, such as restenosis and stent thrombosis [10]. This can lead to better long-term outcomes for patients.

QFR enables precise localization of functionally significant lesions, allowing interventional cardiologists to identify the exact artery segments needing stenting [1,9]. This avoids unnecessary extension of the stent beyond the diseased area. By providing an accurate assessment of the functional significance and exact length of coronary lesions, QFR can lead to the use of shorter stents during PCI [11]. This precision helps prevent unnecessary stenting, reduces the risk of complications, and enhances both the cost-effectiveness and overall outcomes of the procedure [10].

We conducted a prospective experimental study to evaluate the diagnostic efficacy and limitations of QFR during primary and staged angiographies in patients who had already undergone successful culprit artery PCI for STEMI, but who still had angiographically significant stenoses in non-infarct-related arteries. We hope that the obtained results will encourage more frequent use of the QFR method in daily clinical practice, to reduce the number of unnecessary PCIs and associated complications. Therefore, this study aimed to evaluate outcomes from QFR-guided complete revascularization and angiography-guided PCI in 124 patients with STEMI.

Material and Methods

ETHICAL STATEMENT:

Authorization for the study was obtained from the Regional Biomedical Research Ethics Committee, under permission No. BE-2–14. Our study included only those patients who provided informed consent for participation in a biomedical study. During the study, the selected patients were examined and treated according to the research and treatment algorithms applied by the Hospital of Lithuanian University of Health Sciences Kaunas Clinics, recommended by international organizations.

PATIENT SELECTION:

This was a randomized prospective experimental single center study, conducted in the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics (July 2020 to June 2021). All patients admitted to our PCI center within 120 min after onset of symptoms who were diagnosed with STEMI according to the criteria outlined in the European Society of Cardiology guidelines for management of patients presenting with ST-segment elevation, which was released in 2017 [12], underwent index culprit lesion PCI to restore blood flow in the occluded artery, and presented with one or more residual non-culprit stenosis (50–75%) were enrolled into this study (Figure 1). Patients were excluded from the study if mechanical reopening and stenting of the infarct-related artery were unsuccessful; it was decided by the Heart Team that coronary artery bypass grafting would be the most appropriate treatment strategy. In addition, patients with serious comorbidities with unfavorable prognosis that could influence survival within the 1 year were excluded. Finally, patients with circulatory instability, cardiogenic shock, pulmonary edema, and other serious conditions at the time of inclusion in the study were not enrolled in the study. The total of 124 patients met all inclusion and exclusion criteria.

RANDOMIZATION:

After the enrollment to the study, 124 patients were randomized into 1 of 2 groups: (1) QFR-guided PCI (n=62; QFR group) and (2) visual estimation-only guided PCI (n=62; angiography group). Data on patient demographic information, medical history, procedure duration, the amount of contrast used, the number and length of stents, fluoroscopy time were collected from PCI procedure protocols and medical records.

ANGIOGRAPHY-QUIDED PCI:

In the visual estimation-only guided PCI, the coronary arteries were assessed by the interventional cardiologist performing the index procedure, and the angiographies were additionally discussed in interventional cardiologists’ meetings. Angiography-guided non-culprit coronary lesions PCI were performed as a staged procedure at least 3 months after the index PCI.

QFR-GUIDED COMPLETE REVASCULARIZATION:

In the QFR-guided PCI group, QFR analyses were performed using the certified software QAngio-XA 3D, version 2.0 (Medis Medical Imaging Systems, Leiden, The Netherlands) from coronary artery angiograms. In this study, stenoses were deemed hemodynamically significant when the QFR was less than 0.8. All QFR analyses were performed offline twice by an experienced and internationally certified QFR observer, with the results averaged. If the 2 measurements did not match (difference >0.02), a third measurement was conducted, and the 3 results were averaged. All patients were suitable for QFR analyses; hence, none were excluded from this group. Residual hemodynamically significant stenoses, according to QFR, were treated during a staged procedure at least 3 months after the index PCI.

STATISTICAL ANALYSIS:

Statistical analysis was conducted using SPSS 28.0 software. Descriptive statistics were used to summarize the data, with the Kolmogorov-Smirnov test assessing normality. Continuous variables, including the duration of the stenting procedure, fluoroscopy time, contrast volume, number and length of stents implanted, and inpatient treatment time, were analyzed using means, standard deviations, and medians. To compare these variables between the 2 groups, the Mann-Whitney U test (a non-parametric test) was applied. Receiver operating characteristic (ROC) curve analysis was used to determine thresholds for fluoroscopy time and contrast usage, along with calculating odds ratios (OR) and 95% confidence intervals (CI) to assess the likelihood of exceeding these thresholds between groups. The chi-square test was used to compare categorical variables, such as the number of stents implanted and periprocedural complication rates. A significance level of P<0.05 was considered statistically significant.

Results

EVALUATION OF THE DURATION OF THE STENTING PROCEDURE:

When comparing the duration of the stenting procedure between the angiography and QFR method groups, no significant differences were found (U=1857.0, P=0.75). The average duration of the stenting procedure in the angiography group was 40.42±3.76 min (median 32.50 min, interquartile range (IQR) 20–46.25 min), while in the QFR method group, the average duration was 33.63±1.64 min (median 30.0 min, IQR 25–40 min).

EVALUATION OF THE DURATION OF FLUOROSCOPY:

When comparing the duration of fluoroscopy during the stenting procedure between the angiography and QFR method groups, statistically significant differences were found (U=1399.5, P=0.009). The average duration of fluoroscopy during the stenting procedure in the angiography group was 10.88±1.24 min (median 8.0 min, IQR 5.2–13.5 min), whereas in the QFR method group, the average duration was 6.59±0.42 min (median 6.2 min, IQR 4.1–8.4 min) (Figure 2). Based on the ROC test, we determined a fluoroscopy time threshold of 10.4 min for the second stage procedure, considering the groups. The likelihood of the fluoroscopy procedure duration exceeding 10.4 min in the angiography group was, on average, 6.3 times higher than in the QFR method group (OR 6.31, 95% CI 2.36–16.85, P=0.001).

EVALUATION OF THE AMOUNT OF CONTRAST USED:

Statistically significant differences were found in the amount of contrast used during the stenting procedure between the angiography and QFR groups (U=1524.0, P=0.038). The average amount of contrast used in the angiography group was 148.23±9.19 mL (median 120.0 mL, IQR 100–200 mL), while in the QFR method group, the amount of contrast used was 116.45±4.38 mL (median 100 mL, IQR 100–122.5 mL; Figure 3). Based on the ROC test, we determined a threshold for the amount of contrast used during the second stage of the stenting procedure, considering the groups (160 mL). The likelihood of using more than 160 mL of contrast in the angiography group was, on average, 10.8 times higher than in the QFR method group (OR 10.82, 95% CI 3.03–38.57, P=0.001).

EVALUATION OF THE NUMBER OF STENTS IMPLANTED:

Statistically significant differences were identified in the number of stents implanted during the stenting procedure between the angiography and QFR groups (U=1343.5, P=0.002). In the angiography group, an average of 2.26±0.14 stents were implanted (median 2.0 stents, IQR 1–3 stents). In the QFR method group, an average of 1.69±1.0 stents were implanted during the procedure (median 1.5 stents, IQR 1–2 stents; Figure 4). In the QFR group, 50.0% of patients had only 1 stent used during non-culprit lesion PCI, compared with 25.8% of patients in the angiography-guided PCI group (P<0.05). Five stents were used significantly more often in the angiography group than in the QFR group, at 6.5% and 0%, respectively (P<0.05).

EVALUATION OF THE LENGTH OF IMPLANTED STENTS:

Statistically significant differences were found in the length of implanted stents during the stenting procedure between the angiography and QFR groups (U=1203.0, P<0.001). In the angiography group, the average stent length was 47.69±3.11 mm (median 45 mm, IQR 28–60.25 mm; Figure 5). In the QFR method group, the average stent length was 33.18±2.26 mm (median 28 mm, IQR 21.25–43.0 mm).

EVALUATION OF PROCEDURAL AND INPATIENT TREATMENT OUTCOMES:

In our study, we evaluated periprocedural complications, such as coronary artery dissection, perforation, no-reflow phenomenon, stent thrombosis (acute or subacute), and unexpected hemodynamic collapse due to various etiological causes. In assessing the frequency of periprocedural complications during PCI between the angiography and QFR method groups, no significant differences were found, with rates of 3.2% and 1.6%, respectively (P>0.05). No significant differences were found in inpatient treatment time between the angiography and QFR method groups (U=1690.0, P=0.24). In the angiography group, the average inpatient treatment time was 7.47±0.52 days (median – 6.5 days, IQR 5.75–9.0 days). In the QFR method group, the average inpatient treatment time was 7.37±0.70 days (median 6 days, IQR 5–8 days).

Discussion

LIMITATIONS:

While our study offers valuable insights, certain limitations should be acknowledged. First, this was a single-center study, which can limit generalizability. Second, the study’s relatively small sample size can reduce the statistical power. Third, the precision and consistency of QFR measurements rely on the technique and quality of angiographic imaging, which currently requires 2 projections for each vessel. Fourth, procedural bias may have been introduced, as PCI operators were aware of the group assignments. Fifth, the angiography-guided PCI group relied on angiography guidance for PCI lesion assessment, which, despite current guideline recommendations, remains the prevailing standard of care in most catheterization laboratories.

Conclusions

In this randomized, prospective, experimental, single-center study, patients with STEMI who had undergone successful recanalization and stenting of the culprit lesion using QFR-guided PCI of the non-culprit lesion resulted in shorter fluoroscopy time, lower contrast volume, and a smaller number and average length of implanted stents. These findings highlight the potential of QFR to enhance procedural efficiency and reduce unnecessary stenting in clinical practice without compromising patient outcomes.