post-PCI Fractional Flow Reserve Research Articles

Gender differences in coronary artery disease patterns

Abstract Background Gender differences in clinical presentation, natural history, and prognosis of coronary artery disease (CAD) have been reported. Fractional flow reserve (FFR) has also been shown to yield higher values in women than men. However, the gender differences in CAD patterns (focal vs diffuse) defined by coronary physiology remain to be studied. Methods This prospective study was performed at 23 sites and enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 intended to be treated by PCI. All patients underwent a standardized physiological protocol that mandated FFR pullbacks with pullback pressure gradient (PPG) calculation. The aim was to compare CAD patterns, defined by PPG, between genders. Results Overall, 1004 patients were included in the analysis, 236 females (250 vessels) and 768 males (794 vessels). Women were older (69.8 ± 10.3 vs. 67.0 ± 10.1, p <0.001), less frequently smokers (9.7% vs. 18.6%, p = 0.002), had less prior PCI in a non-target vessel (19.1% vs. 30.6%, p = 0.001) and had less prior MIs (14.4% vs. 21.5%, p = 0.021). On the baseline seven-item Seattle Angina Questionnaire (SAQ-7), females reported more physical limitation (70.9 ± 29.5 vs. 80.9 ± 25.1, p < 0.001), more frequent angina (76.7 ± 22.9 vs. 81.5 ± 20.3, p = 0.002) and a lower quality of life (51.8 ± 29.4 vs. 57.8 ± 29.1, p = 0.006) than men for the same degree of flow reduction (FFR 0.69 ± 0.12 vs. 0.67 ± 0.11, p=0.098). In women, the pattern of CAD demonstrated a more focal nature compared to men (PPG 0.65 ± 0.16 vs. 0.61 ± 0.16, p = 0.001). Also, women achieved higher post-PCI FFR (0.88 ± 0.07 vs. 0.87 ± 0.07, p = 0.02). The rate of periprocedural MI was not statistically different between genders (5.1% vs. 5.8%, p = 0.79) Conclusion Among patients with hemodynamically significant CAD, women report more symptoms and lower quality of life. Despite sharing a similar degree of flow impairment, women exhibited a more focal CAD phenotype than men, leading to superior physiological outcomes after PCI.Study flowchartPRO and Phisiology by gender

Comparative analysis of post-PCI fractional flow reserve and quantitative flow ratio in predicting long-term Target Vessel Failure and hard endpoints

Abstract Background The role of functional assessment after angiographically acceptable post-PCI result is debatable. Purpose We sought to investigate the correlation between Fractional Flow Reserve measured directly after drug eluting stent (DES) implantation (post-PCI FFR) and post-PCI Quantitative Flow Ratio (post-PCI QFR), clarify their relationship with clinical parameters, and long-term target vessel failure (TVF: cardiac death (CD), non-fatal target vessel myocardial infarction (MI) and target vessel revascularisation (TVR)), and a composite of CD and MI (CD/MI). Method Coronary arteries that underwent post-PCI FFR measurement at our centre between 2012 and January 2021 were consecutively included in this registry. Post-PCI QFR was calculated blinded to the post-PCI FFR value. We analysed the influence of LAD vs. (non-LAD) location, gender, age, hypertension, diabetes mellitus, hyperlipidemia, indication (acute (ACS) vs. chronic coronary syndrome), stent diameter, in-stent restenosis (ISR) vs. de novo lesion category, estimated glomerular filtration rate, proximal vs. distal lesions, severe aortic stenosis, atrial fibrillation during the procedure (AF), and prior myocardial infarction in the supply area (prior MI) on post-PCI FFR and QFR. Optimal cut-off was determined by ROC curves. Results A total of 400 coronary arteries were analysed. LAD location (p<0.001), male gender (p=0.0029) and smaller stent diameter (p=0.0073) proved to be predictors of a lower post-PCI FFR. LAD location (p=0.001), ISR (p=0.02), distal location (p=0.0019), AF (p=0.042) and prior MI (p=0.029) were predictors of a lower post-PCI QFR. There was a systematic bias in post-PCI QFR compared to post-PCI FFR (bias 0.0614, 95% CI, 0.053 - 0.069). During a median follow-up of 45 months, 31 CD, 20 MI and 35 TVR occurred. Follow-up was complete in 100%. There was a significant inverse correlation between post-PCI FFR and TVF (p<0.001) as well as between post-PCI QFR and TVF (p=0.045). In-stent restenosis (p=0.014) and prior MI (p=0.002) were also predictors of higher TVF rate. The predictors of CD/MI were lower post-PCI FFR (p<0.001), smaller stent diameter (p=0.03), higher age (p=0.031) and ACS indication (p=0.048), whereas post-PCI QFR was not. The best post-PCI FFR cut-off to predict TVF was 0.87 (p<0.0001). There was no single optimal post-PCI QFR cut-off to predict TVF. Conclusion Post-PCI QFR shows a systematic bias compared to post-PCI FFR. Post-PCI FFR is a significant predictor of TVF as well as CD/MI, whereas post-PCI QFR predicts TVF. No significant correlation between post-PCI QFR and CD/MI could be demonstrated. Our findings underscore the importance of considering multiple clinical parameters in predicting long-term outcomes. The best post-PCI FFR cut-off to predict TVF was 0.87. However, there was no single, universally applicable post-PCI QFR threshold to predict TVF.

TCT-219 Comparative Analysis of Post-PCI Fractional Flow Reserve and Quantitative Flow Ratio in Predicting Long-term Target Vessel Failure and Hard Endpoints

TCT-219 Comparative Analysis of Post-PCI Fractional Flow Reserve and Quantitative Flow Ratio in Predicting Long-term Target Vessel Failure and Hard Endpoints

Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Angiography-derived physiological patterns of coronary artery disease: implications with post-stenting physiology and long-term clinical outcomes.

Physiological patterns of coronary artery disease (CAD) have emerged as potential determinants of functional results of percutaneous coronary interventions (PCI) and of vessel-oriented clinical outcomes (VOCE). In this study, we evaluated the impact of angiography-derived physiological patterns of CAD on post-PCI functional results and long-term clinical outcomes. Pre-PCI angiography-derived fractional flow reserve (FFR) virtual pullbacks were quantitatively interpreted and used to determine the physiological patterns of CAD. Suboptimal post-PCI physiology was defined as an angiography-derived FFR value ≤ 0.91. The primary endpoint was the occurrence of VOCE at the longest available follow-up. Six hundred fifteen lesions from 516 patients were stratified into predominantly focal (n = 322, 52.3%) and predominantly diffuse (n = 293, 47.7%). Diffuse pattern of CAD was associated with lower post-PCI angiography-derived FFR values (0.91 ± 0.05 vs. 0.94 ± 0.05; p = 0.001) and larger rate of suboptimal post-PCI physiology (43.0 vs. 22.7%; p = 0.001), as compared to focal CAD. At the median follow-up time of 37months (33-58), post-PCI suboptimal physiology was related to a higher risk of VOCE (16.2% vs. 7.6%; HR: 2.311; 95% CI 1.410-3.794; p = 0.0009), while no significant difference was noted according to baseline physiological pattern. In diffuse disease, the use of intracoronary imaging was associated with a lower incidence of long-term VOCE (5.1% vs 14.8%; HR: 0.313, 95% CI 0.167-0.614, p = 0.030). Suboptimal post-PCI physiology is observed more often in diffusely diseased arteries and it is associated with higher risk of VOCE at follow-up. The use of intravascular imaging might improve clinical outcomes in the setting of diffuse CAD.

Prognostic Implications of Fractional Flow Reserve and Coronary Flow Reserve After Drug-Eluting Stent Implantation.

Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) provides prognostic information, but limited data are available regarding prognostication using post-PCI coronary flow reserve (CFR). In this study we aimed to assess the prognostic value of post-procedural FFR and CFR for target vessel failure (TVF) after PCI. This lesion-based post-hoc pooled analysis of previously published registry data involved 466 patients with chronic coronary syndrome with single-vessel disease who underwent pre- and post-PCI FFR and CFR measurements, and were followed-up to determine the predictors of TVF. The prognostic value of post-PCI CFR and FFR was compared with that of FFR or CFR alone. Post-PCI FFR/CFR discordant results were observed in 42.5%, and 10.3% of patients had documented TVF. Receiver-operating characteristic curve analysis revealed that the optimal cutoff values of post-PCI FFR and CFR to predict the occurrence of TVF were 0.85 and 2.26, respectively. Significant differences in TVF were detected according to post-PCI FFR (≤0.85 vs. >0.85, P=0.007) and post-PCI CFR (<2.26 vs. ≥2.26, P<0.001). Post-PCI FFR ≤0.85 and post-PCI CFR <2.26 were independent prognostic predictors. After PCI completion, discordant results between FFR and CFR were not uncommon. Post-PCI CFR categorization showed incremental prognostic value for predicting TVF independent of post-PCI FFR risk stratification.

Association of Coronary Computed Tomography-Defined Myocardial Bridge With Pre- and Post-Procedural Fractional Flow Reserve in Patients Undergoing Elective Percutaneous Coronary Intervention.

Myocardial bridge (MB) is a common coronary anomaly characterized by a tunneled course through the myocardium. Coronary computed tomography angiography (CCTA) can identify MB. The impact of MB detected by CCTA on coronary physiological parameters before and after percutaneous coronary intervention (PCI) is unknown.Methods and Results: We investigated 141 consecutive patients who underwent pre-PCI CCTA and fractional flow reserve (FFR)-guided elective PCI for de novo single proximal lesions in the left anterior descending artery (LAD). We compared clinical demographics and physiological parameters between patients with and without CCTA-defined MB. MB was identified in 46 (32.6%) patients using pre-PCI CCTA. The prevalence of diabetes was higher among patients with MB. Median post-PCI FFR values were significantly lower among patients with than without MB (0.82 [interquartile range 0.79-0.85] vs. 0.85 [interquartile range 0.82-0.89]; P=0.003), whereas pre-PCI FFR values were similar between the 2 groups. Multivariable linear regression analysis revealed that the presence of MB and greater left ventricular mass volume in the LAD territory were independently associated with lower post-PCI FFR values. Multivariable logistic regression analysis also revealed that the presence of MB and lower pre-PCI FFR values were independent predictors of post-PCI FFR values ≤0.80. CCTA-defined MB independently predicted both lower post-PCI FFR as a continuous variable and ischemic FFR as a categorical variable in patients undergoing elective PCI for LAD.

VALIDATION OF QUANTITATIVE FLOW RATIO DERIVED VIRTUAL ANGIOPLASTY WITH POST–ANGIOPLASTY FRACTIONAL FLOW RESERVE. THE QIMERA–I STUDY

Abstract Backgroud Quantitative flow ratio (QFR) virtual angioplasty with pre–PCI residual QFR showed better results compared with angiographic approach to assess post–PCI functional results. However correlation with pre–PCI residual QFR and post–PCI fractional flow reserve (FFR) is lacking. Methods Multicenter prospective study including consecutive patientswith angiographically 50–90% coronary lesions and positive QFR result. All patients were evaluated with QFR, hyperemic and non–hyperemic pressure ratios (NHPR) before and after the index PCI. Pre–PCI residual QFR (virtual angioplasty) was calculated and compared with post–PCI fractional flow reserve (FFR), QFR and NHPR. Results A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5±10.9 years and 59% of single vessel lesion being the left anterior descending artery in 69%. The mean vessel diameter was 2.82±0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17±0.46. Baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 + 0.08 and 0.82 + 0.11, respectively. Mean post–PCI FFR increased to 0.87 ±0.05 whereas residual QFR had been estimated as 0.95 ± 0.05 showing poor correlation with post–PCI FFR (0.163; 95%CI:0.078–0.386) and a low diagnostic accuracy (30.9%, 95%CI:20–43%). Conclusions In this analysis, the results of QFR–based virtual angioplasty did not seem to accurately correlate with post–PCI FFR.

Physiology- or Imaging-Guided Strategies for Intermediate Coronary Stenosis

Treatment strategies for intermediate coronary lesions guided by fractional flow reserve (FFR) and intravascular ultrasonography (IVUS) have shown comparable outcomes. Identifying low-risk deferred vessels to ensure the safe deferral of percutaneous coronary intervention (PCI) and high-risk revascularized vessels that necessitate thorough follow-up can help determine optimal treatment strategies. To investigate outcomes according to treatment types and FFR and IVUS parameters after FFR- or IVUS-guided treatment. This cohort study included patients with intermediate coronary stenosis from the Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients With Intermediate Stenosis (FLAVOUR) trial, an investigator-initiated, prospective, open-label, multicenter randomized clinical trial that assigned patients into an IVUS-guided strategy (which recommended PCI for minimum lumen area [MLA] ≤3 mm2 or 3 mm2 to 4 mm2 with plaque burden [PB] ≥70%) or an FFR-guided strategy (which recommended PCI for FFR ≤0.80). Data were analyzed from November to December 2022. FFR or IVUS parameters within the deferred and revascularized vessels. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and revascularization at 2 years. A total of 1619 patients (mean [SD] age, 65.1 [9.6] years; 1137 [70.2%] male) with 1753 vessels were included in analysis. In 950 vessels for which revascularization was deferred, incidence of TVF was comparable between IVUS and FFR groups (3.8% vs 4.1%; P = .72). Vessels with FFR greater than 0.92 in the FFR group and MLA greater than 4.5 mm2 or PB of 58% or less in the IVUS group were identified as low-risk deferred vessels, with a decreased risk of TVF (hazard ratio [HR], 0.25 [95% CI, 0.09-0.71]; P = .009). In 803 revascularized vessels, the incidence of TVF was comparable between IVUS and FFR groups (3.6% vs 3.7%; P = .95), which was similar in the revascularized vessels undergoing PCI optimization (4.2% vs 2.5%; P = .31). Vessels with post-PCI FFR of 0.80 or less in the FFR group or minimum stent area of 6.0 mm2 or less or with PB at stent edge greater than 58% in the IVUS group had an increased risk for TVF (HR, 7.20 [95% CI, 3.20-16.21]; P < .001). In this cohort study of patients with intermediate coronary stenosis, FFR- and IVUS-guided strategies showed comparable outcomes in both deferred and revascularized vessels. Binary FFR and IVUS parameters could further define low-risk deferred vessels and high-risk revascularized vessels.

Mis-Alignment of Clinical Goals and Financial Incentives in Coronary Stent Revascularizations Adversely Affects Patient Outcomes

The misalignment of clinical and financial incentives for coronary stent revascularizations (percutaneous coronary interventions, PCI) by the Medicare payor, CMS (Centers for Medicare and Medicaid Services), has adversely affected patient-beneficiaries. Financial incentives, remunerations, encourage performance of inappropriate and unnecessary PCIs. While Fractional Flow Reserve (FFR) can prevent unnecessary PCIs, nevertheless, FFR adoption has not occurred despite documented unequivocal benefits by: (1) identifying a lesion’s ischemic potential, (2) determining need for stent revascularization, (3) replacing the inaccurate physician’s visual estimate of vessel narrowing severity with the nonaligned FFR metric, and (4) replacing the inaccurate angiographic silhouette as the measure of success with post-PCI FFR, which, in addition, supplies critical substantive outcome data. CMS’ payment schedules to physicians, hospitals, and, as a result, medical device vendors, unfortunately, incentivized maintenance of the status quo. If FFR were the requisite determinative that would disqualify ~1/3rd of PCIs, procedures which would become coronary angiograms (CA), then, with present reimbursement schedules, the resulting devastating fiscal headwinds would be problematic for all parties. In contradistinction, CMS savings, considering that 231,000 among the 700,000 potential PCI SVA (Single Vessel Angioplasty) patients, that converted to CA, whose hospital reimbursement is $3,108/case, would range from $1.2- $2.9 billion. However, positively altering the reimbursement schedule for physicians is central. If a PCI became a CA, physician reimbursement would decrease to $228-$394, in contradistinction, a $1,000 increase for FFR guidewire manipulation and data interpretation, plus the $228-$394 for CA performance would increase their payment to $1,200-$1,400/procedure, which is separate from hospital payments. Hospital payments should increase by $1,000-2,000 (i.e., solely profit) above the CA payment of $3,108, plus an added vendor FFR wire payment of $2,500. This total, $6,608-$7,608, is significantly less than hospital PCI+DES (Drug Eluting Stent) of $12,767-$20,127 revascularization payments, which would have been paid for a PCI. For vendors, stent payment losses, selling prices of $600-$1,600/stent, is overcome by (1) the FFR wires manufacturing costs ($200-$300) that approximates 10% of the $2,500 payment (gross profit of 90%), and (2) the significant FFR market expansion of &gt;1 million PCIs and a similar sized CA market with a considerable percentage of undiagnosed coronary artery obliterative disease. This proposal financially incentivizes physicians to perform FFR, and hospitals, without a procedural profit loss, should be financial indifferent to the procedure performed. The mis-alignment of financial incentives is not illusory but can be restored with appropriate alignment that benefits all parties financially, prevents unnecessary PCIs, improves patient outcomes, and reduces Medicare/CMS expenditures by billions.

Validation of Quantitative Flow Ratio-Derived Virtual Angioplasty with Post-Angioplasty Fractional Flow Reserve-The QIMERA-I Study.

Background: Quantitative flow ratio (QFR) virtual angioplasty with pre-PCI residual QFR showed better results compared with an angiographic approach to assess post-PCI functional results. However, correlation with pre-PCI residual QFR and post-PCI fractional flow reserve (FFR) is lacking. Methods: A multicenter prospective study including consecutive patients with angiographically 50-90% coronary lesions and positive QFR results. All patients were evaluated with QFR, hyperemic and non-hyperemic pressure ratios (NHPR) before and after the index PCI. Pre-PCI residual QFR (virtual angioplasty) was calculated and compared with post-PCI fractional flow reserve (FFR), QFR and NHPR. Results: A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5 ± 10.9 years and 59% of single vessel lesions being the left anterior descending artery in 69%. The mean vessel diameter was 2.82 ± 0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17 ± 0.46. The baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 ± 0.08 and 0.82 ± 0.11, respectively. Mean post-PCI FFR increased to 0.87 ± 0.05 whereas residual QFR had been estimated as 0.95 ± 0.05, showing poor correlation with post-PCI FFR (0.163; 95% CI:0.078-0.386) and low diagnostic accuracy (30.9%, 95% CI:20-43%). Conclusions: In this analysis, the results of QFR-based virtual angioplasty did not seem to accurately correlate with post-PCI FFR.

Combined Assessment of Fractional Flow Reserve and Coronary Flow Velocity Reserve after Drug-Eluting Stent Implantation

Coronary flow velocity reserve (CFVR) can be measured noninvasively using stress transthoracic Doppler echocardiography (S-TDE). The prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to investigate the prognostic value of post-PCI CFVR and its additional efficacy to fractional flow reserve (FFR) in patients undergoing elective PCI. A retrospective study was conducted involving 187 consecutive patients with chronic coronary syndrome who underwent elective PCI guided by FFR for the left anterior descending coronary artery. Pre- and post-PCI wire-based FFR and CFVR assessments of the left anterior descending coronary artery using S-TDE were performed in all patients. The association between post-PCI clinical and physiologic parameters and major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, heart failure, and unplanned remote target vessel revascularization, was evaluated. Three-quarters of patients exhibited CFVR increase after PCI, while all patients showed FFR improvement. During a median follow-up period of 1.5years, MACE occurred in 21 patients (11.2%). Among clinical demographics, patients with MACE had higher levels of N-terminal pro-brain natriuretic peptide compared with those without MACE (median, 615pg/mL [interquartile range, 245-1,500pg/mL] vs 180pg/mL [interquartile range, 70-559pg/mL]; P=.010). Post-PCI S-TDE-derived CFVR was lower in patients with MACE, while post-PCI FFR showed a nonsignificant tendency to be lower in patients with MACE. In a multivariable analysis, higher NT-proBNP (adjusted hazard ratio, 1.33; 95% CI, 1.02-1.74; P=.038), post-PCI CFVR ≤ 2.0 (adjusted hazard ratio, 2.93; 95% CI, 1.16-7.40; P=.023), and post-PCI FFR ≤ 0.82 (adjusted hazard ratio, 3.93; 95% CI, 1.52-10.18; P=.005) were independently associated with MACE. In patients with chronic coronary syndrome who underwent successful elective PCI for left anterior descending coronary artery, the combined assessment of S-TDE-derived post-PCI CFVR and post-PCI FFR provided a significant association with the occurrence of MACE.

Long-term association of post stent fractional flow reserve with clinical events

Abstract Background Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with procedural factors in the stented segment and residual disease in the non-stented segment. Even the prognostic value of post-PCI FFR has been reported, its long-term clinical relevance has not been thoroughly investigated. Purpose We sought to investigate the long-term prognostic value of post-PCI FFR and its relative significance on future events in stented and non-stented segments. Methods The International Post-PCI FFR extended registry (NCT04684043) followed the 2,200 patients who underwent PCI and measured post-PCI FFR between June 2011 and May 2018. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction (TVMI), and target vessel revascularization (TVR) at 5 years. The secondary outcomes were a composite of cardiac death or TVMI at 5 years. Results The median value of post-PCI FFR of target vessels was 0.89 (IQR 0.84-0.93). The optimal cut-off value of post-PCI FFR for predicting TVF was 0.81, and that for predicting cardiac death or TVMI was 0.76, respectively. The cumulative incidence of TVF was significantly higher in the low post-PCI group (20.5%) than in the high post-PCI FFR group (10.3%) (adjusted hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.56-2.86, p&amp;lt;0.001). The cumulative incidence of cardiac death or TVMI was also significantly higher in the low post-PCI FFR group (7.3%) than in the high post-PCI FFR group (3.2%) (adjusted HR 2.34, 95% CI 1.12-4.91, p=0.024). Landmark analysis at 2 years showed that the impact of post-PCI FFR on TVF was consistently found during the first 2 years (adjusted HR of low post-PCI FFR 2.22, 95% CI 1.54-3.21, p&amp;lt;0.001) and thereafter (adjusted HR of low post-PCI FFR 1.96, 95% CI 1.14-3.36, p&amp;lt;0.001). However, the impact of post-PCI FFR on cardiac death or TVMI was more significant after 2 years of follow-up (adjusted HR of low post-PCI FFR 2.01, 95% CI 0.66-6.11, p=0.217 for the first 2 years and adjusted HR of low-post PCI FFR 2.81, 95% CI 1.04-7.60, p=0.042). The cumulative incidence of TVR was 9.5% for 5 years, and 61.0% of TVRs occurred in the stented segment. However, the proportion of TVRs in the non-stented segment increased along with the decrease of post-PCI FFR (35.3% in post-PCI FFR more than 0.90, 34.1% in post-PCI FFR 0.81-0.90, 43.8% in post-PCI FFR 0.71-0.80, and 66.7% in post-PCI FFR 0.70 and less than 0.70, p-for trend&amp;lt;0.001). Conclusions The long-term outcome results of the Internation Post-PCI FFR Extended registry showed that the prognostic impact of post-PCI FFR on TVF was consistently found along with the follow-up. However, that of post-PCI FFR on cardiac death or TVMI was more prominent during the late period of follow-up. In addition, clinical event distribution was different according to post-PCI FFR values.

Predictors of successful post-PCI optimization in vessels with post-PCI fractional flow reserve &amp;lt;0.90: findings from the FFR REACT trial

Abstract Introduction Recent studies demonstrated a strong relation between suboptimal post-PCI fractional flow reserve (FFR) and clinical outcome. The feasibility of post-PCI FFR optimization and its impact on future clinical outcome remains topic of debate. Purpose The aim of the present substudy of the FFR REACT trial was to identify predictors of 1) absolute FFR increase following optimization and 2) successful functional optimization (final FFR ≥0.90). Methods The FFR REACT trial was a single-center, investigator initiated, randomized controlled trial including patients with (un)stable angina or non-ST segment elevation myocardial infarction and angiographically successful PCI. Following a post-PCI FFR &amp;lt;0.90, patients were randomized to intravascular ultrasound (IVUS)-guided optimization according to a dedicated optimization protocol (intervention arm) or no further treatment (control arm). In case of PCI optimization, FFR and IVUS were repeated to evaluate the optimization result. The present analysis included all patients randomized to IVUS-guided optimization, who actually underwent PCI optimization, and who had pre- and post-optimization FFR values available. We performed multivariate linear and logistic regression models to identify predictors of absolute FFR increase and FFR ≥0.90 following optimization. Results A total of 145 patients were allocated to the IVUS-guided optimization arm with 152 vessels having a post-PCI FFR &amp;lt;0.90 (mean post-PCI FFR: 0.83±0.05), of which 104 vessels (68.4%) underwent additional treatment after IVUS evaluation. Paired FFR measurements (pre- and post-optimization) were available in 100/104 optimized vessels. The mean absolute change in FFR was 0.03±0.06 (p&amp;lt;0.001), and 20/100 (20%) vessels achieved a final FFR ≥0.90. Both left anterior descending arteries (LAD) (mean change = -0.033, 95%CI -0.055- -0.010, p=0.004) and higher post-PCI FFR values (mean change per 0.01 unit increase = -0.005, 95%CI -0.007 - -0.004, p&amp;lt;0.001) were associated with lower changes in FFR following optimization. Independent predictors of achieving a final FFR ≥0.90 were higher post-PCI FFR values (OR 1.26 per 0.01 unit increase, 95%CI 1.06-1.51, p=0.009) and non-LAD vessels (OR 5.72, 95%CI 1.73-18.94, p=0.004). Conclusions Within the FFR REACT trial, we observed that the likelihood of improvement in final FFR values was driven by the initial post-PCI FFR values (before optimization) and the location of the target vessel, with non-LAD lesion location being a significant predictor of FFR increase.

TDE-derived impaired post-PCI Coronary flow velocity reserve predicts MACE in patients who underwent LAD PCI

Abstract Background Coronary flow velocity reserve (CFVR) can be obtained noninvasively by stress transthoracic Doppler echocardiography (S-TDE). However, prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. Purpose This study aimed to investigate the relationship between post-PCI CFVR and major adverse cardiac event (MACE). Methods This study prospectively included 200 patients with stable coronary artery disease who were scheduled for elective PCI of de novo, single, functionally significant left anterior descending (LAD) lesions at a single tertiary-care center between April 2019 and November 2022. All patients underwent fractional flow reserve (FFR)-guided elective PCI. Exclusion criteria were patients with previous coronary artery bypass graft surgery, left main coronary artery disease and periprocedural myocardial infarction as defined by the fourth universal definition of myocardial infarction. Eligible patients underwent pre- (1 day before) and post-procedural (3 days after) LAD coronary flow assessments by stress-TDE. CFVR was calculated as the ratio of the hyperemic peak diastolic flow velocity to the basal peak diastolic flow velocity. We also excluded the patients with suboptimal S-TDE imaging. Association between post-PCI physiological parameters and MACE (composite of cardiac death, myocardial infarction, heart failure and target vessel revascularization) were evaluated. Results A total of 174 patients were included in the final analysis after successful LAD PCI. MACE occurred in twenty-one (12.0%) patients during the follow-up (1.9 [0.9-2.5] years). Clinical demographics were similar in patients with versus without MACE. Post-PCI S-TDE-derived CFVR was lower in patients with versus without MACE (P = 0.023), while post-PCI FFR values tended to be lower in patients with versus without MACE, albeit not significant (P = 0.077). Receiver-operating characteristic curve analysis revealed that the optimal cut-off values of post-PCI FFR and post-PCI CFVR values to predict MACE were 0.83 and 1.70, respectively. Significant differences in the MACE were detected according to post-PCI FFR (≤ 0.83 versus &amp;gt; 0,83: 17.9 % versus 6.7 %, P = 0.035) and post-PCI CFVR (&amp;lt; 1.70 versus ≥ 1.70: 33.3% versus 8.2%, P = 0.001). On a multivariable Cox-proportional hazard analysis, patients with post-PCI CFVR &amp;lt; 1.70 had an increased risk for MACE (adjusted hazard ratio [HR] 4.75, 95% confidence interval [CI] 1.98-11.38, P &amp;lt; 0.001), along with post-PCI FFR ≤ 0.83 (adjusted HR 2.78, 95% CI 1.07-7.20, P=0.035). Conclusions In patients who underwent successful elective PCI for LAD, S-TDE-derived impaired post-PCI CFVR and post-PCI FFR were independently associated with MACE.

Impact of myocardial bridge defined by computed tomographic coronary angiography on fractional flow reserve after elective percutaneous coronary intervention

Abstract Background Myocardial bridge (MB) is a common anomaly of epicardial coronary artery that courses through myocardium. MB can be identified by computed tomographic coronary angiography (CTCA) or invasive coronary angiography (ICA). However, its relevance to coronary physiological parameters remains unknown. Purpose This observational study aimed to explore how MBs affect physiological parameters in patients with chronic coronary syndrome before and after revascularization. Methods We investigated 172 consecutive patients who underwent preprocedural CTCA and elective fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in left anterior descending artery (LAD). We compared patient characteristics, angiographic, and pre- and post-PCI physiological parameters in patients with versus without MB. Results We identified MB in 70 (40.7%) and 23 (13.3%) patients by CTCA and ICA, respectively. CTCA detected the presence of MB with a sensitivity of 100% and a specificity of 33% when ICA-defined MB was regarded as a reference standard. Longer MB (adjusted odds ratio 1.18 [95% confidence interval 1.05-1.33], P &amp;lt; 0.01) and smaller left ventricular myocardial mass volume in whole LAD territory (adjusted odds ratio 0.93 [95% confidence interval 0.89-0.98], P&amp;lt;0.01) were associated with ICA detectability of MB. Older age and higher frequency of diabetes mellitus were observed in patients with MB compared with those without MB. Pre-PCI FFR values were not associated with a presence of MB regardless of either CTCA- or ICA-defined MB. On the other hand, post-PCI FFR values were significantly lower in patients with versus without MB by CTCA (0.82 [0.80-0.86] vs. 0.86 [0.82-0.89], P&amp;lt;0.01), while no significant difference was observed in post-PCI FFR between patients with and without ICA-defined MB (0.82 [0.81-0.84 vs. 0.84 [0.80-0.88], P=0.08). Multivariable linear regression analysis revealed that a presence of CTCA-defined long MB (≥25mm) (adjusted β coefficient = -0.040, P&amp;lt;0.01) and greater myocardial mass volume in whole LAD territory (adjusted β coefficient = -0.0004, P&amp;lt;0.01) were independently associated with lower post-PCI FFR. Conclusion A presence of MB was an independent predictor of lower post-PCI FFR after successful and elective PCI for LAD.

Clinical and vessel characteristics associated with hard outcomes after PCI and their combined prognostic implications

Abstract Background While clinical outcomes after percutaneous coronary intervention (PCI) have improved in recent decades, cardiac death or myocardial infarction (MI) still occurs in patients undergoing contemporary PCI. An integrative risk model for post-PCI hard clinical endpoints incorporating clinical risk factors, angiographic and physiological vessel characteristics has not been established. Purpose To identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve (FFR) measurement after drug eluting stent (DES) implantation, 2,081 patients with available 10 clinical characteristics (age, sex, clinical diagnosis at index procedure, diabetes, hypertension, dyslipidemia, smoking history, chronic kidney disease [CKD], prior myocardial infarction, left ventricular ejection fraction [LVEF]) and 8 vessel characteristics (target vessel, reference vessel diameter, % diameter stenosis, minimum lumen diameter [MLD], post-PCI % diameter stenosis, post-PCI MLD, total stent length in the target vessel, and post-PCI FFR) were analyzed. The least absolute shrinkage and selection operator (LASSO) model was applied for feature selection. The primary outcome was cardiac death or target vessel-MI at 2-years. Results The mean age of patients was 64.2±10.2 years, and the mean angiographic % diameter stenosis was 63.9±14.3%. Among 10 clinical and 8 vessel features, 4 adverse clinical characteristics (ACCs; age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction &amp;lt;50%) and 2 adverse vessel characteristics (AVCs; post-PCI FFR ≤0.80 and total stent length ≥54 mm) were selected by the LASSO model. All ACCs and AVCs were independent predictors for the primary outcome (HR 3.33 [95% CI 1.34 – 8.25], P =0.009 for age ≥65 years; HR 2.62 [1.22 – 5.65], P =0.014 for diabetes; HR 5.95 [2.52 – 14.1], P &amp;lt;0.001 for CKD; HR 2.91 [1.17 – 7.20], P =0.021 for LVEF &amp;lt;50%; HR 3.79 [1.73 – 8.28], P &amp;lt;0.001 for post-PCI FFR ≤0.80; HR 2.42 [1.08 – 5.39], P =0.031 for total stent length ≥54 mm). The number of AVCs had additive predictability for the primary endpoint to that of ACCs (AUC 0.72 vs 0.78, P =0.03), and vice versa (AUC 0.68 vs 0.78, P =0.03). The cumulative event rate increased in the order of none, either, and both of ACCs ≥2 and AVCs ≥1 (0.3%, 2.4%, and 5.3%, P-for-trend &amp;lt;0.01) (Figure). Conclusions In patients undergoing DES implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target vessel-MI. Since these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification.

Association between myocardial bridge with transthoracic doppler echocardiography-defined physiological indices and fractional flow reserve before and after elective percutaneous coronary intervention

Abstract Background A myocardial bridge (MB) is a coronary variant in which an epicardial coronary artery courses through myocardium. MB can be identified by computed tomographic coronary angiography (CTCA) or invasive coronary angiography (ICA), which is known to be common in left anterior descending artery (LAD). Transthoracic Doppler echocardiography (TDE) noninvasively provides coronary flow information. Purpose We aimed to investigate the physiological impact of myocardial bridge on coronary flow dynamics assessed by adenosine-induced stress-TDE before and after elective percutaneous coronary intervention (PCI). Methods We examined 93 consecutive patients treated with fractional flow reserve (FFR)-guided elective PCI who underwent pre-PCI CTCA and pre- and post-PCI stress-TDE. We compared patient characteristics, angiographic, physiological data, and stress-TDE-defined coronary flow parameters in patients with versus without MB. Results We identified MB in 40 (43.0%) and 15 (16.1%) patients by CTCA and ICA, respectively. All MBs diagnosed by ICA were identified by CTCA. Longer MB was associated with the detectability by ICA. Older age and higher frequency of diabetes mellitus were observed in patients with CTCA-defined MB compared with those without. Pre-PCI FFR was similar in patients with versus without CTCA-defined MB (0.69 [0.61-0.73] vs. 0.69 [0.61-0.75], P=0.92), while post-PCI FFR was significantly lower in patients with versus without CTCA-defined MB (0.82 [0.78-0.86] vs. 0.84 [0.82-0.88], P=0.01). Pre- and Post- PCI hyperemic systolic peak flow velocity (SPV) by stress-TDE was higher in patients with versus without MB by CTCA (36 [26-43] m/s vs. 30 [23-34] m/s, P=0.03 and 38 [32-52] m/s vs. 33 [20-39] m/s, P=0.02, respectively). Pre-PCI hyperemic diastolic peak flow velocity (DPV) by stress-TDE was not significantly different between the 2 groups (49 [39-64] m/s vs. 45 [34-55] m/s, P=0.12), while post-PCI hyperemic DPV was higher in patients with versus without CTCA-defined MB (73 [60-85] m/s vs. 63 [50-81] m/s, P=0.03). Conclusion In patients undergoing elective PCI for LAD, a presence of CTCA-defined MB was associated with higher pre- and post-PCI hyperemic SPV and an acceleration of hyperemic DPV after the PCI. Impact of systolic compression by MB on hyperemic DPV at the distal segment accelerated by the treatment of upstream stenosis may lead to lower post-PCI FFR compared with patients without MB.

Coronary Physiology Guidance vs Conventional Angiography for Optimization of Percutaneous Coronary Intervention: The AQVA-II Trial

BackgroundThe debate surrounding the efficacy of coronary physiological guidance compared with conventional angiography in achieving optimal post–percutaneous coronary intervention (PCI) fractional flow reserve (FFR) values persists. ObjectivesThe primary aim of this study was to demonstrate the superiority of physiology-guided PCI, using either angiography or microcatheter-derived FFR, over conventional angiography-based PCI in complex high-risk indicated procedures (CHIPs). The secondary aim was to establish the noninferiority of angiography-derived FFR guidance compared with microcatheter-derived FFR guidance. MethodsPatients with obstructive coronary lesions and meeting CHIP criteria were randomized 2:1 to receive undergo physiology- or angiography-based PCI. Those assigned to the former were randomly allocated to angiography- or microcatheter-derived FFR guidance. CHIP criteria were long lesion (>28 mm), tandem lesions, severe calcifications, severe tortuosity, true bifurcation, in-stent restenosis, and left main stem disease. The primary outcome was invasive post-PCI FFR value. The optimal post-PCI FFR value was defined as >0.86. ResultsA total of 305 patients (331 study vessels) were enrolled in the study (101 undergoing conventional angiography-based PCI and 204 physiology-based PCI). Optimal post-PCI FFR values were more frequent in the physiology-based PCI group compared with the conventional angiography-based PCI group (77% vs 54%; absolute difference 23%, relative difference 30%; P < 0.0001). The occurrence of the primary outcome did not differ between the 2 physiology-based PCI subgroups, demonstrating the noninferiority of angiography- vs microcatheter-derived FFR (P < 0.01). ConclusionsIn CHIP patients, procedural planning and guidance on the basis of physiology (through either angiography- or microcatheter-derived FFR) are superior to conventional angiography for achieving optimal post-PCI FFR values. (Physiology Optimized Versus Angio-Guided PCI [AQVA-II]; NCT05658952)

Impact of Post-PCI FFR Stratified by Coronary Artery

BackgroundLow fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated. ObjectivesThis study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery. MethodsWe performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. ResultsOverall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005). ConclusionsThe LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels.