Non-randomized comparison between revascularization and deferral for intermediate coronary stenosis with abnormal fractional flow reserve and preserved coronary flow reserve.

Limited data are available regarding comparative prognosis after percutaneous coronary intervention (PCI) versus deferral of revascularization in patients with intermediate stenosis with abnormal fractional flow reserve (FFR) but preserved coronary flow reserve (CFR). From the International Collaboration of Comprehensive Physiologic Assessment Registry (NCT03690713), a total of 330 patients (338 vessels) who had coronary stenosis with FFR ≤ 0.80 but CFR > 2.0 were selected for the current analysis. Patient-level clinical outcome was assessed by major adverse cardiac events (MACE) at 5 years, a composite of all-cause death, target-vessel myocardial infarction (MI), or target-vessel revascularization. Among the study population, 231 patients (233 vessels) underwent PCI and 99 patients (105 vessels) were deferred. During 5 years of follow-up, cumulative incidence of MACE was 13.0% (31 patients) without significant difference between PCI and deferred groups (12.7% vs. 14.0%, adjusted HR 1.301, 95% CI 0.611-2.769, P = 0.495). Multiple sensitivity analyses by propensity score matching and inverse probability weighting also showed no significant difference in patient-level MACE and vessel-specific MI or revascularization. In this hypothesis-generating study, there was no significant difference in clinical outcomes between PCI and deferred groups among patients with intermediate stenosis with FFR ≤ 0.80 but CFR > 2.0. Further study is needed to confirm this finding.Clinical Trial Registration: International Collaboration of Comprehensive Physiologic Assessment Registry (NCT03690713; registration date: 10/01/2018).S

Safety of coronary revascularization deferral based on fractional flow reserve and instantaneous wave-free ratio in patients with chronic kidney disease

Background: The safety of revascularization deferral according to pressure wire examination in patients with chronic kidney disease (CKD) has not been fully established. Methods: From a retrospective cohort of 439 patients in whom revascularization was deferred after physiological assessment, we examined the incidence of patient-oriented composite endpoint (POCE: all-cause death, myocardial infarction [MI] and unplanned revascularization) in patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) and without it. Results: At 4 years of follow-up, the primary endpoint was met by 25.0% of patients with CKD and by 14.4% of patients without CKD (hazard ratio [HR] 1.56, 95% confidence interval [CI] 0.96–2.53, p = 0.071). The incidence of POCE was even higher in patients with an eGFR < 30 mL/min/1.73 m2: 43.8% (HR 3.10, 95% CI 1.08–8.92, p = 0.036). However, no differences were observed in the incidence of MI (4.2% vs. 4.4% in non-CKD), target vessel revascularization (5.8% vs. 5.9%), and target vessel MI (0.8% vs. 4.6%). Conclusions: Patients with CKD in whom pressure-wire evaluation led to deferral of coronary revascularization develop more POCE in the long term, compared to patients with normal renal function. However, the increase in POCE in patients with CKD was seldom related to deferred vessels, thus suggesting an epiphenomenon of an intrinsically higher cardiovascular risk of CKD patients

Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements includi

Changes in microvascular resistance following percutaneous coronary intervention - From the ILIAS global registry

BACKGROUND: Microvascular resistance (MR) has prognostic value in acute and chronic coronary syndromes following percutaneous coronary intervention (PCI), however anatomic and physiologic determinants of the relative changes of MR and its association to target vessel failure (TVF) has not been investigated previously. This study aims to evaluate the association between changes in MR and TVF. METHODS: This is a sub-study of the Inclusive Invasive Physiological Assessment in Angina Syndromes (ILIAS) registry which is a global multi-centre initiative pooling lesion-level coronary pressure and flow data. RESULTS: Paired pre-post PCI haemodynamic data were available in n = 295 vessels out of n = 828 PCI treated patients and of these paired data on MR was present in n = 155 vessels. Vessels were divided according to increase vs. decrease % in microvascular resistance following PCI (ΔMR % ≤ 0 vs. ΔMR > 0%). Decreased microvascular resistance ΔMR % ≤ 0 occurred in vessels with lower pre-PCI fractional flow reserve (0.67 ± 0.15 vs. 0.72 ± 0.09 p = 0.051), coronary flow reserve (1.9 ± 0.8 vs. 2.6 ± 1.8 p 0%. In a cox regression model ΔMR % > 0 was associated with increased rate of TVF (hazard ratio 95% CI 3.6 [1.2; 10.3] p = 0.018). CONCLUSION: Increased MR post-PCI was associated with lesions of less severe hemodynamic influence at baseline and higher rates of TVF at follow-up

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry

Aims: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. Methods and results: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef. - 2.88, 95% confidence interval (CI): -3.05 - 2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). Conclusion: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease

Impact of sex on the assessment of the microvascular resistance reserve

Background: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. Aim: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. Methods: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. Results: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47–0.96, p = 0.027) and men (HR 0.84, 0.74–0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. Conclusion: The MRR seems to be equally applicable in both women and men with stable coronary artery disease

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p <0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe

Sex differences in prevalence and outcomes of the different endotypes of chronic coronary syndrome in symptomatic patients undergoing invasive coronary angiography: Insights from the global ILIAS invasive coronary physiology registry

Background and aims: The management of chronic coronary syndrome (CCS) is informed by studies predominantly including men. This study investigated the relationship between patients sex and different endotypes of CCS, including sex-specific clinical outcomes. Methods: In patients with CCS undergoing coronary angiography, invasive Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) were measured. Patients were stratified into groups: 1) obstructive coronary artery disease (oCAD) (FFR≤0.80, no revascularization), 2) undergoing revascularization, 3) non-obstructive coronary artery disease with coronary microvascular dysfunction (CMD) (FFR>0.80, CFR≤2.5), and 4) non-obstructive coronary artery disease without CMD (FFR>0.80 and CFR>2.5). Results: 1836 patients (2335 vessels) were included, comprising 1359 (74.0%) men and 477 (26.0%) women. oCAD was present in 14.1% and was significantly less prevalent in women than in men (10.3% vs 15.5%, respectively p < 0.01). Revascularization was present in 30.9% and was similarly prevalent in women and men (28.2% vs. 31.9%, respectively p = 0.13). CMD was present in 24.2% and was significantly more prevalent in women than men (28.6% vs 22.6%, respectively p < 0.01). Normal invasive measurements were found in 564 patients (33.0% women vs 30.0% men, p = 0.23). Male sex was associated with an increased risk of target vessel failure compared to women (HR.1.89, 95% CI 1.12–3.18, p = 0.018), regardless of CCS-endotype. Conclusions: Sex differences exist in the prevalence and outcomes of different endotypes of CCS in symptomatic patients undergoing invasive coronary angiography. In particular, oCAD (and subsequent revascularization) were more prevalent in men. Conversely, CMD was more prevalent in women. Overall, men experienced a worse cardiovascular outcome compared to women, independent of any specific CCS endotype

Association between patient age, microcirculation, and coronary stenosis assessment with fractional flow reserve and instantaneous wave-free ratio

© 2022 Wiley Periodicals LLCObjectives: To investigate the effect of aging on coronary stenosis functional assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). Background: Limited data exist regarding the impact of patient age on these coronary pressure indices. Methods: We analyzed 514 patients with coronary stenosis interrogated with intravascular physiology. The influence of patient age on FFR, iFR, and microcirculation-related indices was investigated. Vessel-oriented composite outcome (VOCO) was assessed in the FFR-based deferred population according to iFR, coronary flow reserve (CFR), and age. Results: FFR increased (r = 0.128, p = 0.004), iFR remained unchanged (r = −0.001, p = 0.980), and CFR decreased (r = −0.095, p = 0.001) with patient age. Relationship between FFR and CFR differed across age groups (r = 0.263 in &lt;60 years old vs. r = 0.124 in ≥60 years old, p = 0.0056), whereas iFR correlated to CFR similarly regardless age (r = 0.283 in &lt;60 years old vs. r = 0.219 in ≥60 years old, p = 0.3781). No differences were found on angiographic stenosis severity (%DS 47.4 in &lt;60 years old and 49.8 in ≥60 years old, p = 0.317). At 5 years, FFR-based revascularisation deferral in patients ≥60 years old was associated with more VOCO when either iFR (25%) or CFR (16.9%) were abnormal, compared to patients with normal iFR (6.3%) or normal CFR (4.6%) (log-rank p &lt; 0.001). This difference in clinical outcomes was not observed in younger patients. Conclusions: FFR values increased progressively with patient age, potentially associated with age-related changes in the coronary microcirculation. Conversely, iFR values remained unchanged across the patient age spectrum. In ≥60 years old patients with revascularisation deferral based on FFR, both abnormal iFR and CFR values were associated with worse long-term patient outcomes.N