Effects of age on microvascular function in patients with normal coronary arteries.

BACKGROUND: It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. AIMS: Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. METHODS: In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rµ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). RESULTS: The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rµ (Rµ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rµ (Rµ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). CONCLUSIONS: There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Prognostic Value of Microvascular Resistance Reserve After Percutaneous Coronary Intervention in Patients With Myocardial Infarction.

BACKGROUND: The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. METHODS: From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n = 1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. RESULTS: Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95% CI: 2.31-7.50; P < 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. CONCLUSIONS: MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study.

BACKGROUND AND AIMS: Microvascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). METHODS: In this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. RESULTS: Among 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). CONCLUSIONS: Our study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

The Influence Of Epicardial Resistance On Microvascular Resistance Reserve.

BACKGROUND: The optimal index of microvascular function should be specific for the microvascular compartment. Yet, coronary flow reserve (CFR), despite being widely used to diagnose coronary microvascular dysfunction (CMD), is influenced by both epicardial and microvascular resistance. Conversely, microvascular resistance reserve (MRR) adjusts for fractional flow reserve (FFR), and thus is theoretically independent of epicardial resistance. OBJECTIVES: We tested the hypothesis that MRR, unlike CFR, is not influenced by increasing epicardial resistance, and thus is a more specific index of microvascular function. METHODS: In a cohort of 16 patients that had undergone proximal left anterior descending artery stenting, we created four grades of artificial stenosis (no stenosis, mild, moderate, and severe) using a coronary angioplasty balloon inflated to different degrees within the stent. For each stenosis grade, we calculated CFR and MRR using continuous thermodilution (64 measurements of each) in order to assess their response to changing epicardial resistance. RESULTS: Graded balloon inflation resulted in a significant sequential decrease in mean FFR (no stenosis: 0.82 ±0.05; mild: 0.72 ±0.04; moderate: 0.61 ±0.05; severe: 0.48 ±0.09, p<0.001). This translated into a linear decrease in mean hyperaemic coronary flow (no stenosis: 170.5 ±66.8 ml/min; mild: 149.8 ±58.8 ml/min; moderate: 124.4 ±53.0 ml/min; severe: 94.0 ±45.2 ml/min, p<0.001). CFR exhibited a marked linear decrease with increasing stenosis (no stenosis: 2.5 ±0.9; mild: 2.2 ±0.8; moderate: 1.8 ±0.7; severe: 1.4 ±0.6), corresponding to a decrease of 0.3 for a decrease in FFR of 0.1 (p<0.001). In contrast, MRR exhibited a negligible decrease across all stenosis grades (no stenosis: 3.0 ±1.0; mild: 3.0 ±1.0; moderate: 2.9 ±1.0; severe: 2.8 ±1.0), corresponding to a decrease of just 0.05 for a decrease in FFR of 0.1 (p<0.001). CONCLUSION: MRR, unlike CFR, is minimally influenced by epicardial resistance, and thus should be considered the more specific index of microvascular function. This suggests that MRR can also reliably evaluate microvascular function in patients with significant epicardial disease.

Measuring Absolute Coronary Flow and Microvascular Resistance by Thermodilution: JACC Review Topic of the Week.

Diagnosing coronary microvascular dysfunction remains challenging, primarily due to the lack of direct measurements of absolute coronary blood flow (Q) and microvascular resistance (Rµ). However, there has been recent progress with the development and validation of continuous intracoronary thermodilution, which offers a simplified and validated approach for clinical use. This technique enables direct quantification of Q and Rµ, leading to precise and accurate evaluation of the coronary microcirculation. To ensure consistent and reliable results, it is crucial to follow a standardized protocol when performing continuous intracoronary thermodilution measurements. This document aims to summarize the principles of thermodilution-derived absolute coronary flow measurements and propose a standardized method for conducting these assessments. The proposed standardization serves as a guide to ensure the best practice of the method, enhancing the clinical assessment of the coronary microcirculation.

Prehospital risk assessment and direct transfer to a percutaneous coronary intervention centre in suspected acute coronary syndrome.

OBJECTIVE: Prehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation. METHODS: Prospective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days. RESULTS: A total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17-101) hours vs 20 (5-44) hours, p<0.001) and length of hospital admission (3 (2-5) days vs 2 (1-4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (€5599 (2978-9625) vs €4899 (2278-5947), p=0.02). CONCLUSION: Prehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation. TRIAL REGISTRATION: NCT05243485.

The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data.

BACKGROUND: Despite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. OBJECTIVES: The aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. METHODS: In a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. RESULTS: In total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. CONCLUSIONS: In this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

Impact of Post-PCI FFR Stratified by Coronary Artery.

BACKGROUND: Low 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. OBJECTIVES: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery. METHODS: We 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. RESULTS: Overall, 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). CONCLUSIONS: The 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.

Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Disease: FAME 3 Trial.

BACKGROUND: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). OBJECTIVES: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). METHODS: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. RESULTS: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. CONCLUSIONS: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate.

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Continuous Versus Bolus Thermodilution-Derived Coronary Flow Reserve and Microvascular Resistance Reserve and Their Association With Angina and Quality of Life in Patients With Angina and Nonobstructive Coronaries: A Head-to-Head Comparison.

Background Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) are physiological parameters to assess coronary microvascular dysfunction. CFR and MRR can be assessed using bolus or continuous thermodilution, and the correlation between these methods has not been clarified. Furthermore, their association with angina and quality of life is unknown. Methods and Results In total, 246 consecutive patients with angina and nonobstructive coronary arteries from the multicenter Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT) were investigated. The 36-item Short Form Health Survey Quality of Life and Seattle Angina questionnaires were completed by 153 patients before the invasive measurements. CFR and MRR were measured consecutively with bolus and continuous thermodilution. Mean continuous thermodilution-derived coronary flow reserve (CFRabs) was significantly lower than mean bolus thermodilution-derived coronary flow reserve (CFRbolus) (2.6±1.0 versus 3.5±1.8; P<0.001), with a modest correlation (ρ=0.305; P<0.001). Mean continuous thermodilution-derived microvascular resistance reserve (MRRabs) was also significantly lower than mean bolus thermodilution-derived MRR (MRRbolus) (3.1±1.1 versus 4.2±2.5; P<0.001), with a weak correlation (ρ=0.280; P<0.001). CFRbolus and MRRbolus showed no correlation with any of the angina and quality of life domains, whereas CFRabs and MRRabs showed a significant correlation with physical limitation (P=0.005, P=0.009, respectively) and health (P=0.026, P=0.012). In a subanalysis in patients in whom spasm was excluded, the correlation further improved (MRRabs versus physical limitation: ρ=0.363; P=0.041, MRRabs versus physical health: ρ=0.482; P=0.004). No association with angina frequency and stability was found. Conclusions Absolute flow measurements using continuous thermodilution to calculate CFRabs and MRRabs weakly correlate with, and are lower than, the surrogates CFRbolus and MRRbolus. Absolute flow parameters showed a relationship with physical complaints. No relationship with angina frequency and stability was found.

Titanium-Nitride-Oxide-Coated vs Everolimus-Eluting Stents in Acute Coronary Syndrome: 5-Year Clinical Outcomes of the TIDES-ACS Randomized Clinical Trial.

Importance: Titanium-nitride-oxide (TiNO)-coated stents show faster strut coverage compared with drug-eluting stents without excessive intimal-hyperplasia observed in bare metal stents. It is important to study long-term clinical outcomes after treatment of patients with an acute coronary syndrome (ACS) by TiNO-coated stents, which are neither drug-eluting stents nor bare metal stents. Objective: To compare the rate of main composite outcome of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization at 5 years in patients with ACS randomized to receive either a TiNO-coated stent or a third-generation everolimus-eluting stent (EES). Design, Setting, and Participants: This multicenter, randomized, controlled, open-label trial was conducted in 12 clinical sites in 5 European countries and enrolled patients from January 2014 to August 2016. Patients presenting with ACS (ST-segment elevation MI, non-ST-segment elevation MI, and unstable angina) with at least 1 de novo lesion were randomized to receive either a TiNO-coated stent or an EES. The present report analyzes the long-term follow-up for the main composite outcome and its individual components. Analysis took place between November 2022 to March 2023. Main outcome: The primary end point was a composite of cardiac death, MI, or target lesion revascularization at 12-month follow-up. Results: A total of 1491 patients with ACS were randomly assigned to receive either TiNO-coated stents (989 [66.3%]) or EES (502 [33.7%]). The mean (SD) age was 62.7 (10.8) years, and 363 (24.3%) were female. At 5 years, the main composite outcome events occurred in 111 patients (11.2%) in the TiNO group vs 60 patients (12%) in the EES group (hazard ratio [HR], 0.94; 95% CI, 0.69-1.28; P = .69). The rate of cardiac death was 0.9% (9 of 989) vs 3.0% (15 of 502) (HR, 0.30; 95% CI, 0.13-0.69; P = .005), the rate of MI was 4.6% (45 of 989) vs 7.0% (35 of 502) (HR, 0.64; 95% CI, 0.41-0.99; P = .049), the rate of stent thrombosis was 1.2% (12 of 989) vs 2.8% (14 of 502) (HR, 0.43; 95% CI, 0.20-0.93; P = .034), and the rate of target lesion revascularization was 7.4% (73 of 989) vs 6.4% (32 of 502) (HR, 1.16; 95% CI, 0.77-1.76; P = .47) in the TiNO-coated stent arm and in the EES arm, respectively. Conclusion and relevance: In this study, patients with ACS had a main composite outcome that was not different 5 years after TiNO-coated stent or EES. Trial Registration: ClinicalTrials.gov Identifier: NCT02049229.

Microvascular Resistance Reserve to Assess Microvascular Dysfunction in ANOCA Patients.

BACKGROUND: Microvascular resistance reserve (MRR) is a new index to assess coronary microvascular (dys)function, which can be easily measured invasively using continuous thermodilution. In contrast to coronary flow reserve (CFR), MRR is independent of epicardial coronary disease and hemodynamic variations. Its measurement is accurate, reproducible, and operator independent. OBJECTIVES: The aim of this study was to establish the range of normal values for MRR and to determine an optimal cutoff point. METHODS: In this exploratory study in 214 patients with angina and no obstructive coronary artery disease, after excluding significant epicardial disease, all physiological parameters, such as fractional flow reserve, index of microvascular resistance, CFR, absolute blood flow, absolute microvascular resistance, and MRR, were measured. On the basis of concordant positive or concordant negative results of index of microvascular resistance and CFR, subgroups of patients were defined with high probability of either normal (n = 122) or abnormal (n = 24) microcirculatory function, and MRR was studied in these groups. RESULTS: Mean MRR in the "normal" group was 3.4 compared with a mean MRR of 1.9 in the "abnormal" group; these values were significantly different between the groups. MRR >2.7 ruled out coronary microvascular dysfunction (CMD) with a certainty of 96%, whereas MRR <2.1 indicated the presence of CMD with a similar high certainty of 96%. CONCLUSIONS: MRR is a suitable index to distinguish the presence or absence of CMD in patients with angina and no obstructive coronary artery disease. The present data indicate that an MRR of 2.7 virtually excludes the presence of CMD, while an MRR value <2.1 confirms its presence.

Changes in absolute flow, myocardial resistance and FFR after chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Randomised studies of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) have shown inconsistent outcomes, suggesting incomplete understanding of this cohort and their coronary physiology. To address this shortcoming, we designed a prospective observational study to measure the recovery of absolute coronary blood flow following successful CTO PCI Aims: We sought to identify patient and procedural characteristics associated with a favourable physiological outcome after CTO PCI. METHODS: Consecutive patients with a CTO subtending viable myocardium underwent PCI utilising contemporary techniques and the hybrid algorithm. Immediately after PCI, and at 3-month follow-up, physiological measurements were performed utilising continuous thermodilution. RESULTS: A total of 81 patients were included with a mean age of 63.6±8.9 years, and 66 (81.5%) were male. Physiological measurements of absolute coronary blood flow in the CTO vessel increased by 30% (p<0.001) and microvascular resistance reduced by 16% (p<0.001) from immediately post-CTO PCI to follow-up assessment. Fractional flow reserve increased by 0.02 (p=0.015) in the same period. Prior coronary artery bypass graft (CABG) and a higher estimated glomerular filtration rate (eGFR) were associated with a larger change in absolute flow. An extraplaque strategy was associated with a smaller change in absolute flow. CONCLUSIONS: Post-CTO PCI, there is a continued augmentation in absolute coronary blood flow and reduction in microvascular resistance from baseline to follow-up at 3 months. Prior CABG and a higher baseline eGFR were predictors of a larger change in absolute coronary flow, whilst an extraplaque final wire path strategy predicted a smaller change. Lastly, the patient characteristics and comorbidities had a larger influence than procedural factors on the observed change in absolute flow.

Prognostic Implications of Fractional Flow Reserve After Coronary Stenting: A Systematic Review and Meta-analysis.

Importance: Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is generally considered to reflect residual disease. Yet the clinical relevance of post-PCI FFR after drug-eluting stent (DES) implantation remains unclear. Objective: To evaluate the clinical relevance of post-PCI FFR measurement after DES implantation. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant published articles from inception to June 18, 2022. Study Selection: Published articles that reported post-PCI FFR after DES implantation and its association with clinical outcomes were included. Data Extraction and Synthesis: Patient-level data were collected from the corresponding authors of 17 cohorts using a standardized spreadsheet. Meta-estimates for primary and secondary outcomes were analyzed per patient and using mixed-effects Cox proportional hazard regression with registry identifiers included as a random effect. All processes followed the Preferred Reporting Items for Systematic Review and Meta-analysis of Individual Participant Data. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel myocardial infarction (TVMI), and target vessel revascularization (TVR). The secondary outcome was a composite of cardiac death or TVMI at 2 years. Results: Of 2268 articles identified, 29 studies met selection criteria. Of these, 28 articles from 17 cohorts provided data, including a total of 5277 patients with 5869 vessels who underwent FFR measurement after DES implantation. Mean (SD) age was 64.4 (10.1) years and 4141 patients (78.5%) were men. Median (IQR) post-PCI FFR was 0.89 (0.84-0.94) and 690 vessels (11.8%) had a post-PCI FFR of 0.80 or below. The cumulative incidence of TVF was 340 patients (7.2%), with cardiac death or TVMI occurring in 111 patients (2.4%) at 2 years. Lower post-PCI FFR significantly increased the risk of TVF (adjusted hazard ratio [HR] per 0.01 FFR decrease, 1.04; 95% CI, 1.02-1.05; P < .001). The risk of cardiac death or MI also increased inversely with post-PCI FFR (adjusted HR, 1.03; 95% CI, 1.00-1.07, P = .049). These associations were consistent regardless of age, sex, the presence of hypertension or diabetes, and clinical diagnosis. Conclusions and Relevance: Reduced FFR after DES implantation was common and associated with the risks of TVF and of cardiac death or TVMI. These results indicate the prognostic value of post-PCI physiologic assessment after DES implantation.

Prognostic Value of Measuring Fractional Flow Reserve After Percutaneous Coronary Intervention in Patients With Complex Coronary Artery Disease: Insights From the FAME 3 Trial.

BACKGROUND: We evaluate the prognostic value of measuring fractional flow reserve (FFR) after percutaneous coronary intervention (post-PCI FFR) and intravascular imaging in patients undergoing PCI for 3-vessel coronary artery disease in the FAME 3 trial (Fractional Flow Reserve versus Angiography for Multivessel Evaluation). METHODS: The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with coronary artery bypass grafting in patients with multivessel coronary artery disease. PCI was not noninferior with respect to the primary end point of death, myocardial infarction, stroke, or repeat revascularization at 1 year. Post-PCI FFR data were acquired on a patient and vessel-related basis. Intravascular imaging guidance was tracked. The primary end point is a comparison of target vessel failure (TVF) defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 1 year based on post-PCI FFR values. Cox regression with robust SEs was used for analysis. RESULTS: Of the 757 patients randomized to PCI, 461 (61%) had post-PCI FFR measurement and 11.1% had intravascular imaging performed. The median post-PCI FFR was 0.89 [IQR' 0.85-0.94]. On a vessel-level, post-PCI FFR was found to be a significant predictor of TVF univariately (hazard ratio=0.67 [95% CI' 0.48-0.93] for 0.1 unit increase, P=0.0165). On a patient-level, the single lowest post-PCI FFR value was also found to be a significant predictor of TVF univariately (hazard ratio=0.65 [95% CI' 0.48-0.89] for 0.1 unit increase, P=0.0074). Post-PCI FFR was an independent predictor of TVF in multivariable analysis adjusted for key clinical parameters. Outcomes were similar between patients who had intravascular imaging guidance and those who did not. CONCLUSIONS: Post-PCI FFR measurement was a significant predictor of TVF on a vessel and patient level and an independent predictor of outcomes in a population with complex 3-vessel coronary artery disease eligible for coronary artery bypass grafting. The limited use of intravascular imaging did not affect outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.