Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

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.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

Functional coronary angiography for the assessment of the epicardial vessels and the microcirculation.

Over the last decade, steady progress has been made in the ability to assess coronary stenosis relevance by merging computerised analyses of angiograms with fluid dynamic modelling. The new field of functional coronary angiography (FCA) has attracted the attention of both clinical and interventional cardiologists as it anticipates a new era of facilitated physiological assessment of coronary artery disease, without the need for intracoronary instrumentation or vasodilator drug administration, and an increased adoption of ischaemia-driven revascularisation. This state-of-the-art review performs a deep dive into the foundations and rationale behind FCA indices derived from either invasive or computed angiograms. We discuss the currently available FCA systems, the evidence supporting their use, and the specific clinical scenarios in which FCA might facilitate patient management. Finally, the rapidly growing application of FCA to the diagnosis of coronary microvascular dysfunction is discussed. Overall, we aim to provide a state-of-the-art review not only to digest the achievements made so far in FCA, but also to enable the reader to follow the many publications and developments in this field that will likely take place in years to come.

Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study.

Background: The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease-Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI). Objectives: The goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy. Methods: A Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country. Results: From the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively. Conclusions: Based on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Ischemia With Nonobstructive Coronary Artery Disease: Concept, Assessment, and Management.

In daily clinical practice, physicians often encounter patients with angina or those with evidence of myocardial ischemia from noninvasive tests but not having obstructive coronary artery disease. This type of ischemic heart disease is referred to as ischemia with nonobstructive coronary arteries (INOCA). INOCA patients often suffer from recurrent chest pain without adequate management and are associated with poor clinical outcomes. There are several endotypes of INOCA, and each endotype should be treated based on its specific underlying mechanism. Therefore, identifying INOCA and discriminating its underlying mechanisms are important issues and of clinical interest. Invasive physiologic assessment is the first step in the diagnosis of INOCA and discriminating the underlying mechanism; additional provocation tests help physicians identify the vasospastic component in INOCA patients. Comprehensive information acquired from these invasive tests can provide a template for mechanism-specific management for patients with INOCA.

Long-term prognostic implications of hemodynamic and plaque assessment using coronary CT angiography.

BACKGROUND AND AIMS: Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA). METHODS: Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFRCT) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFRCT, wall shear stress (WSS), change in FFRCT across the lesion (ΔFFRCT), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF). RESULTS: During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11-4.86], p = 0.025), and FFRCT[V] (per 0.1 increase, HR 0.56 [95% CI 0.37-0.84], p = 0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100 dyne/cm2 increase, HR 1.43 [1.09-1.88], p = 0.010), LAPV[L] (per 10 mm3 increase, HR 3.81 [1.16-12.5], p = 0.028), and ΔFFRCT[L] (per 0.1 increase, HR 1.39 [1.02-1.90], p = 0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p < 0.05). CONCLUSIONS: Vessel- and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion-level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value.

Combined Assessment of FFR and CFR for Decision Making in Coronary Revascularization: From the Multicenter International ILIAS Registry.

OBJECTIVES: The aim of this study was to demonstrate the clinical implications of combined assessment of fractional flow reserve (FFR) and coronary flow reserve (CFR). BACKGROUND: Combined assessment of FFR and CFR allows detailed characterization of pathophysiology in chronic coronary syndromes. Data on the clinical implications of distinct FFR and CFR patterns are limited, leading to uncertainty regarding their relevance. METHODS: Patients with chronic coronary syndromes and obstructive coronary artery disease were selected from the multicenter ILIAS (Inclusive Invasive Physiological Assessment in Angina Syndromes) registry. Patients were classified into 4 groups on the basis of FFR ≤0.80 and CFR <2.0. The endpoint was the 5-year target vessel failure (TVF) rate. RESULTS: A total of 2,143 patients with 2,725 lesions were included. Compared with normal FFR/normal CFR, low FFR/low CFR carried the highest risk for TVF (HR: 5.4; 95% CI: 3.2-9.3; P < 0.001), significantly higher than in revascularized vessels (P = 0.007). Discordance, with either low FFR/normal CFR or normal FFR/low CFR, was associated with increased TVF rates compared with normal FFR/normal CFR (low FFR/normal CFR: HR: 3.5 [95% CI: 2.2-5.4; P < 0.001]; normal FFR/low CFR: HR: 3.0 [95% CI: 1.9-4.7; P < 0.001]). No difference in 5-year TVF was observed between the 2 discordant groups (P = 0.57) or between the discordant groups and the revascularized group (P = 0.26 vs low FFR/normal CFR; P = 0.60 vs normal FFR/low CFR). CONCLUSIONS: Impaired coronary hemodynamics are uniformly associated with increased 5-year TVF rates. Nonrevascularized vessels with discordant FFR and CFR are associated with 5-year event rates that are equivalent to those of vessels that undergo revascularization, whereas vessels with combined low FFR and CFR exhibit event rates that are significantly higher than after revascularization. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234).

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

OBJECTIVES: 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 <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 <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 <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 < 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.

Coronary microcirculation assessment using functional angiography: Development of a wire-free method applicable to conventional coronary angiograms.

OBJECTIVES: We aimed to develop a novel wire- and adenosine-free microcirculatory resistive index from functional angiography (angio-IMR) to estimate coronary microcirculatory resistance, and to investigate how this method can improve clinical interpretation of physiological stenosis assessment with quantitative flow ratio (QFR). BACKGROUND: Hyperemic index of coronary microcirculatory resistance (IMR) is a widely used tool to assess microcirculatory dysfunction. However, the need of dedicated intracoronary wire and hyperemia limits its adoption in clinical practice. METHODS: We performed our study in two separate stages: (1) development of a formula (angio-IMR) to estimate IMR from resting angiograms and aortic pressure (Pa), and (2) validation of the method in a clinical population using invasively measured IMR as reference. Additionally, QFR diagnostic performance was assessed considering angio-IMR values. RESULTS: We developed the formula: angio-IMR = (Pa-[0.1*Pa])*QFR*e-Tmn (where e-Tmn is an estimation of hyperaemic mean transit time) and validated it in 115 vessels (104 patients). Angio-IMR correlated well with IMR (Spearman's rho = 0.70, p < 0.001). Sensitivity, specificity, positive and negative predictive value, accuracy and area under the curve of angio-IMR to predict IMR were 87.5% (73.2-95.8), 85.3% (75.3-92.4), 76.1% (64.5-84.8), 92.8% (84.9-96.7), 85% and 0.90 (0.83-0.95), respectively. False positive QFR measurements decreased from 19.5% to 8.5% when angio-IMR was incorporated into the QFR interpretation workflow. CONCLUSIONS: Estimation of IMR without physiology wire and adenosine is feasible. Coronary microcirculatory dysfunction causing high IMR can be ruled-out with high confidence in vessels with low angio-IMR. Awareness of angio-IMR contributes to a better clinical interpretation of functional stenosis assessment with QFR.

Physiologic Assessment after Coronary Stent Implantation.

The presence of myocardial ischemia is a prerequisite for the benefit of coronary revascularization. In the cardiac catheterization laboratory, fractional flow reserve and non-hyperemic pressure ratios are used to define the ischemia-causing coronary stenosis, and several randomized studies showed the benefit of physiology-guided coronary revascularization. However, physiology-guided revascularization does not necessarily guarantee the relief of ischemia. Recent studies reported that residual ischemia might exist in up to 15-20% of cases after angiographically successful percutaneous coronary intervention (PCI). Therefore, post-PCI physiologic assessment is necessary for judging the appropriateness of PCI, detecting the lesions that may benefit from additional PCI, and risk stratification after PCI. This review will focus on the current evidence for post-PCI physiologic assessment, how to interpret these findings, and the future perspectives of physiologic assessment after PCI.

Role of Post-Stent Physiological Assessment in a Risk Prediction Model After Coronary Stent Implantation.

OBJECTIVES: The aim of this study was to develop a risk model incorporating clinical, angiographic, and physiological parameters to predict future clinical events after drug-eluting stent implantation. BACKGROUND: Prognostic factors after coronary stenting have not been comprehensively investigated. METHODS: A risk model to predict target vessel failure (TVF) at 2 years was developed from 2,200 patients who underwent second-generation drug-eluting stent implantation and post-stent fractional flow reserve (FFR) measurement. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. A random survival forest model with automatic feature selection by minimal depth analysis was used for risk model development. RESULTS: During 2 years of follow-up, the cumulative incidence of TVF was 5.9%. From clinical, angiographic, and physiological parameters, 6 variables were selected for the risk model in order of importance within the model as follows: total stent length, post-stent FFR, age, post-stent percentage diameter stenosis, reference vessel diameter, and diabetes mellitus. Harrell's C index of the random survival forest model was 0.72 (95% confidence interval [CI]: 0.62 to 0.82). This risk model showed better prediction ability than models with clinical risk factors alone (Harrell's C index = 0.55; 95% CI: 0.41 to 0.59; p for comparison = 0.005) and with clinical risk factors and angiographic parameters (Harrell's C index = 0.65; 95% CI: 0.52 to 0.77; p for comparison = 0.045). When the patients were divided into 2 groups according to the median of total stent length (30 mm), post-stent FFR and total stent length showed the highest variable importance in the short- and long-stent groups, respectively. CONCLUSIONS: A risk model incorporating clinical, angiographic, and physiological predictors can help predict the risk for TVF at 2 years after coronary stenting. Total stent length and post-stent FFR were the most important predictors. (International Post PCI FFR Registry; NCT04012281).

Long-term Patient Prognostication by Coronary Flow Reserve and Index of Microcirculatory Resistance: International Registry of Comprehensive Physiologic Assessment.

BACKGROUND AND OBJECTIVES: Recent guideline recommends evaluation using of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with functionally insignificant stenosis. We evaluated clinical implications of CFR and IMR in patients with high fractional flow reserve (FFR) and deferred revascularization. METHODS: A total of 867 patients (1,152 vessels) consigned to deferred revascularization who underwent comprehensive physiologic assessments were enrolled. Patients with high FFR (>0.80) were categorized by CFR (≤2) and IMR (≥23 U). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction (MI), and revascularization at 5 years. RESULTS: Patients with low CFR (≤2) showed significantly greater risk of POCO than those with high CFR (>2) in both high-FFR (p=0.024) and low-FFR (p=0.034) groups. In patients with high FFR, those with low CFR and high IMR (overt microvascular disease) displayed the greatest risk of POCO overall (p=0.015), surpassing those with high CFR and low IMR (HR, 2.873; 95% CI, 1.476-5.594; p=0.002) and showing significantly greater risk of cardiac death or MI (HR, 5.662; 95% CI, 1.984-16.154; p=0.001). Overt microvascular disease was independently associated with POCO in the high-FFR population (HR, 2.282; 95% CI, 1.176-4.429; p=0.015). CONCLUSION: Among patients with deferred revascularization, those with low CFR showed significantly greater risk of POCO than those with high CFR, regardless of FFR. In patients with high FFR, those with overt microvascular disease showed significantly greater risk of POCO and cardiac death or MI at 5-year, compared with the others. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03690713.

Effect of Sex Difference of Coronary Microvascular Dysfunction on Long-Term Outcomes in Deferred Lesions.

OBJECTIVES: This study investigated the sex difference of long-term cardiovascular outcomes on coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with deferred coronary artery lesions. BACKGROUND: Coronary microvascular dysfunction is associated with poorer long-term outcomes. It can be assessed by CFR and the IMR. METHODS: The study prospectively enrolled 434 patients (133 women and 301 men) and analyzed CFR, IMR, fractional flow reserve, and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular event(s) (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up. The study protocol was approved by the Institutional Review Board or Ethics Committee at each participating center, and all patients provided written informed consent. The study protocol was in accordance with the Declaration of Helsinki. RESULTS: Women had milder epicardial disease compared with men (fractional flow reserve: 0.91 [interquartile range (IQR): 0.87 to 0.96] vs. 0.90 [IQR: 0.86 to 0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR: 2.08 to 3.90] vs. 3.20 [IQR: 2.20 to 4.31]; p = 0.006) due to a shorter resting mean transit time, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio: 4.58; 95% confidence interval: 1.85 to 11.30; p = 0.011) which was not seen in women. CONCLUSIONS: There was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).

Sex Differences in Long-Term Outcomes in Patients With Deferred Revascularization Following Fractional Flow Reserve Assessment: International Collaboration Registry of Comprehensive Physiologic Evaluation.

Background Sex-specific differences may influence prognosis after deferred revascularization following fractional flow reserve (FFR) measurement. This study sought to investigate the sex differences in long-term prognosis of patients with deferred revascularization following FFR assessment. Methods and Results A total of 879 patients (879 vessels) with deferred revascularization with FFR >0.75 who underwent FFR and coronary flow reserve measurements were enrolled from 3 countries (Korea, Japan, and Spain). Long-term outcomes were assessed in 649 men and 230 women by the patient-oriented composite outcome (POCO, a composite of any death, any myocardial infarction, and any revascularization). We applied inverse-probability weighting based on propensity scores to account for differences at baseline between women and men (age, hyperlipidemia, diabetes mellitus, diameter stenosis, lesion length, multivessel disease, FFR, coronary flow reserve. The median follow-up duration was 1855 days (745-1855 days). Median FFR values were 0.88 (0.83-0.93) in men and 0.89 (0.85-0.94) in women, respectively. The occurrences of POCO were significantly high in men compared with that in women (10.5% versus 4.2%, P=0.007). Kaplan-Meier analysis revealed that women had a significantly lower risk of POCO (χ2=7.2, P=0.007). Multivariate COX proportional hazards regression analysis revealed that age, male, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve were independent predictors of POCO. After applying IPW, the hazard ratio of males for POCO was 2.07 (95% CI, 1.07-4.04, P=0.032). Conclusions This large multinational study reveals that long-term outcome differs between women and men in favor of women after FFR-guided revascularization deferral. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02186093.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

BACKGROUND: Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. METHODS: We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. RESULTS: We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. CONCLUSIONS: The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.