Higher Fractional Flow Reserve Research Articles

Clinical outcomes of patients with deferred revascularisation based on fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) negative coronary artery lesions in Pakistani population.

To assess long-term clinical outcomes and factors associated with target vessel revascularisation in patients with deferred revascularisation based on negative fractional flow reserve and negative instantaneous wave-free ratio. The longitudinal, retrospective study was conducted from July 1, 2020, to January 1, 2022, at the Aga Khan University Hospital, Karachi, and comprised medical records from January 2012 to January 2020 of patients with deferred revascularisation having intermediate to severe coronary lesions on coronary angiogram and had negative fractional flow reserve >0.80 or instantaneous wave-free ratio >0.89 and had not undergone immediate or planned revascularisation on the basis of negative physiological assessment. Data was collected from the institutional records, while final follow-up was taken by reviewing the medical records or telephonic interviews regarding any major adverse cardiac event after the index procedure. Data was analysed using Stata 14.2. Of the 345 patients, 245(71%) were males. The overall mean age was 62±11 years. There were 194(56%) patients who presented with stable angina and 151(44%) presented with acute coronary syndrome. Mean fractional flow reserve was 0.87±0.04 and mean instantaneous wave-free ratio was 0.93±0.03. Multivessel disease was present in 223(65%) patients. Median follow-up period was 29 months (IQR: 24-36 months). Major adverse cardiovascular events occurred in 22(6%) patients, and target vessel revascularisation was required in 11(3%). Diabetes and percentage of stenosis were found to be independent predictors of major adverse cardiovascular events (p<0.05). Deferral of revascularisation and opting for medical treatment for coronary artery stenosis with higher fractional flow reserve or instantaneous wave-free ratio could be considered a safe and reasonable strategy.

Diagnostic performance of pressure-bounded coronary flow reserve.

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79%, sensitivity of 83%, specificity of 78%, positive predictive value of 48%, negative predictive value of 95%. The discordance presenting CFRthermo < 2.0 and pb-CFR ≥ 2.0 was associated with diffuse disease (P < 0.001). The discordance presenting CFRthermo ≥ 2 and pb-CFR < 2 was associated with a high FFR (P = 0.002). Pb-CFR showed moderate correlation and poor agreement with CFRthermo. Pb-CFR might be reliable in excluding epicardial coronary artery disease and microcirculatory disorders.

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.

Characteristics and correlation between FFR and RFR of non-culprit lesions in acute myocardial infarction

Background: While resting-full cycle ratio (RFR) is strongly correlated with fractional flow reserve (FFR), it has been extensively examined in stable coronary artery disease. However, there is a lack of evaluation regarding non-culprit lesions in patients with acute myocardial infarction (AMI). Objectives: To investigate the clinical characteristics and to identify the correlation and discordance between FFR and RFR among AMI patients with non-culprit lesions. Methods: A retrospective cohort study was conducted in 44 AMI patients who underwent percutaneous coronary intervention (PCI) for culprit lesions and &gt; 90% stenosis non-culprit lesions. With non-culprit stenosis from 50 - 90%, 23 patients had simultaneous measurements of both FFR and RFR, and 17 patients underwent PCI based on FFR ≤ 0.8. Results: Approximately 79.5% of patients exhibited a presence of two or more risk factors associated with coronary artery disease. In 44 culprit lesions, 40.9% of cases located in the RCA branch, while in 46 nonculprit lesions, 61.4% of cases were found in the LAD branch. The average FFR among 44 patients was 0.82 ± 0.13. There was a significant improvement in FFR after PCI (0.89 ± 0.07) compared to pre-PCI (0.70 ± 0.11) in 17 patients with p &lt; 0.001. The mean RFR among the 23 patients was 0.84 ± 0.12. Among 12 patients with positive RFR, RFR after PCI (0.95 ± 0.04) was higher than pre-PCI (0.78 ± 0.13) with p = 0.002. Furthermore, pre-PCI RFR showed a strong positive correlation with FFR (r = 0.662, p = 0.001). The discordant rate between RFR and FFR was 26.8%. The discordant rate of FFR and RFR measurements was 26.1%. Additionally, the left anterior descending artery (LAD) was assumed as a predictor of discordance in the high FFR group (FFR &gt; 0.80) and low RFR group (RFR ≤ 0.89). Conclusion: The low discordance rate and strong correlation between FFR and RFR suggest their complementary roles in the assessment of intermediate non-culprit lesions in patients with AMI. Key words: fractional flow reserve, resting full-cycle ratio, non-culprit lesion, correlation, acute myocardial infarction.

Sex Differences in Fractional Flow Reserve– or Intravascular Ultrasound–Guided Percutaneous Coronary Intervention

BackgroundA recent randomized trial reported fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy was noninferior to the intracoronary ultrasound (IVUS)-guided PCI strategy with respect to clinical outcomes with fewer revascularizations. ObjectivesThis study sought to investigate the sex differences in treatment and clinical outcomes according to physiology- or imaging-guided PCI strategies. MethodsIn this secondary analysis of the FLAVOUR (Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI) trial, the impact of sex on procedural characteristics, PCI rate, and outcomes according to different strategies and treatment types (PCI vs deferral of PCI) was analyzed. The primary outcome was target vessel failure (TVF) at 24 months, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. ResultsOf 1,619 patients, 30% were women. Compared with men, women had a smaller minimal lumen area, smaller plaque burden, and higher FFR. They had a lower PCI rate (40.8% vs 47.9%; P = 0.008), which was mainly contributed by FFR guidance. Overall, women showed a lower TVF rate (2.4% vs 4.5%). According to the treatment type, the cumulative incidence of TVF was lower in women than in men among those with the deferral of PCI (1.7% vs 5.2%). However, this trend was not observed in patients who underwent PCI. In both women and men, there were no differences in clinical outcomes between the FFR- and IVUS-guided strategies. ConclusionsIn cases of intermediate stenosis, despite receiving fewer interventions, women had more favorable outcomes than men. The use of FFR led to a lower PCI rate but had a similar prognostic value compared with IVUS in both women and men.

Sex Differences in Murray Law-Based Quantitative Flow Ratio Among Patients With Intermediate Coronary Lesions.

Background The Murray law-based quantitative flow ratio (μQFR) is a novel technique that simulates fractional flow reserve (FFR) from a single angiographic view. However, the impact of sex differences on the diagnostic performance of μQFR has not been investigated. Methods and Results In this study, FFR and μQFR were assessed in 497 intermediate stenoses (30%-70% by visual estimation) from 460 patients (34.3% female). Physiological significance was defined as FFR ≤0.80 or μQFR ≤0.80. After adjusting for potential confounders, female sex was independently associated with higher FFR (P=0.048 and 0.026, respectively) and μQFR (P=0.001 for both) in both fully adjusted and stepwise backward models. μQFR provided superior diagnostic accuracy compared with angiography alone for detecting FFR ≤0.80 in both women (area under the curve, 0.93 [95% CI, 0.88-0.97] versus 0.80 [95% CI, 0.73-0.86]; P=0.001) and men (area under the curve, 0.88 [95% CI, 0.84-0.92] versus 0.73 [95% CI, 0.68-0.78]; P<0.001), with comparable performance between the sexes (P=0.175). In the multivariable analysis, sex was not a significant factor contributing to the overall disagreement between FFR and μQFR. Conclusions Regardless of angiographic stenosis severity, women tend to have higher FFR and μQFR values than men. Furthermore, μQFR performs similarly well in both sexes and offers improved diagnostic accuracy over angiography alone, indicating its potential as a reliable, wire-free tool to identify functional ischemia.

Insufficient adenosine-induced hyperemia is a major determinant of discordance between non-hyperemic pressure ratio and fractional flow reserve

Adenosine occasionally overestimates fractional flow reserve (FFR) values (i.e., insufficient adenosine-induced hyperemia), leading to low non-hyperemic pressure ratios (NHPR)–high FFR discordance. We investigated the impact of insufficient adenosine-induced hyperemia on NHPR–FFR discordance and the reclassification of functional significance. We measured resting distal-to-aortic pressure ratio (Pd/Pa) and FFR by using adenosine (FFRADN) and papaverine (FFRPAP) in 326 patients (326 vessels). FFRADN overestimation was calculated as FFRADN − FFRPAP. We explored determinants of low Pd/Pa − high FFRADN discordance (Pd/Pa ≤ 0.92 and FFRADN > 0.80) versus high Pd/Pa − low FFRADN discordance (Pd/Pa > 0.92 and FFRADN ≤ 0.80). Reclassification of functional significance was defined as FFRADN > 0.80 and FFRPAP ≤ 0.80. Multivariable analysis identified FFRADN overestimation (p = 0.002) and heart rate at baseline (p = 0.048) as independent determinants of the low Pd/Pa–high FFRADN discordance. In the low Pd/Pa–high FFRADN group (n = 26), papaverine produced a further decline in the FFR value in 21 vessels (81%) compared with FFRADN, and the reclassification was observed in 17 vessels (65%). Insufficient adenosine-induced hyperemia is a major determinant of the low resting Pd/Pa–high FFR discordance. Physicians should bear in mind that the presence of low NHPR–high FFR discordance may indicate a false-negative FFR result.

Personalized computational estimation of relative change in coronary blood flow after percutaneous coronary intervention in short-term and long-term perspectives

Abstract Coronary artery disease is the leading cause of mortality worldwide, accounting for 12.8% of all deaths. Although the clinical benefits of treating stenosis with percutaneous coronary intervention (PCI) have been extensively demonstrated, residual myocardial ischemia remains in about 30–50% of patients even after a formally successful PCI. We apply previously developed and validated 1D model of haemodynamics, which distributes terminal hydraulic resistance based on the diameters of the parent vessels and Murray’s law by a recursive algorithm. In our new model the terminal resistance is decreased according to a transmural perfusion ratio increase. In contrast to our previous work we calculate the transmural perfusion ratio for personally defined zones. Thus, peripheral hydraulic resistance of myocardial perfusion is personalized based on patient data, whichwere extracted from computed tomography perfusion images. The model serves as a computational tool for simulating pre- to post-PCI changes in coronary haemodynamics of four patients. We simulate fractional flow reserve (FFR), coronary flow reserve (CFR), instantaneous wave-free ratio (iFR), average flow in selected arteries in hyperemic and rest conditions before PCI and after PCI immediately after the surgery (in a short-term) and in a long-term (several months) perspectives. We conclude that high FFR and iFR values in short-term and long-term perspectives are not necessary correlate with CFR improvement and long-term blood flow recovery in coronary arteries.

Predictive value of post-percutaneous coronary intervention fractional flow reserve: a systematic review and meta-analysis.

We aimed to investigate the relationship between post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and clinical outcome using a systematic review with a study-level meta-analysis. MEDLINE, Embase, and CENTRAL were systematically searched for articles with clinical follow-up reporting mean or median final post-PCI FFR. The main outcome was a composite of major adverse cardiac events (MACE) including all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Meta-regression analyses were performed on mean post-PCI FFR values. A total of 62 studies with 12340 patients and 12923 stented vessels were included, with follow-ups ranging from 1 to 89 months. Post-PCI FFR was not continuously associated with the rate of 1-year MACE or 1-year TVR using meta-regression models accounting for heterogeneous follow-up lengths. For studies comparing high vs. low post-PCI FFR, low post-PCI FFR was associated with high risk ratio for MACE {1.97 [95% confidence interval (CI):1.45-2.67]}, all-cause death [1.59 (95% CI: 1.08-2.34)], MI [3.18 (95% CI: 1.84-5.50)], TVR [2.08 (95% CI: 1.63-2.65)] and angina status [2.50 (95% CI: 1.53-4.06)] using different optimal cut-off values spanning from 0.80 to 0.95. We found no clear continuous association between post-PCI FFR and clinical outcomes in this systematic study-level meta-analysis. In a subset of studies investigating binary classification, high post-PCI FFR was associated with a better clinical outcome than low post-PCI FFR.We investigated the relationship between post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and rate of major adverse cardiac events (MACE), including all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR), using a systematic review and study-level meta-analysis, pooling 12340 patients from 62 studies. Mean post-PCI FFR was not continuously associated with a 1-year MACE rate accounting for heterogenous follow-up lengths. Still, the risk ratio favoured high post-PCI FFR for reduced MACE, all-cause death, MI, TVR, and better angina status using different cut-offs.

Clinical Validation of a Virtual Planner for Coronary Interventions Based on Coronary CT Angiography

BackgroundLow fractional flow reserve (FFR) values after percutaneous coronary intervention (PCI) carry a worse prognosis than high post-PCI FFR values. Therefore, the ability to predict post-PCI FFR might play an important role in procedural planning. Post-PCI FFR values can now be computed from pre-PCI coronary computed tomography angiography (CTA) using the fractional flow reserve derived from coronary computed tomography angiography revascularization planner (FFRCT Planner). ObjectivesThe aim of this study was to validate the accuracy of the FFRCT Planner. MethodsIn this multicenter, investigator-initiated, prospective study, patients with chronic coronary syndromes and significant lesions based on invasive FFR ≤0.80 were recruited. The FFRCT Planner was applied to the fractional flow reserve derived from coronary computed tomography angiography (FFRCT) model, simulating PCI. The primary objective was the agreement between the predicted post-PCI FFR by the FFRCT Planner and measured post-PCI FFR. Accuracy of the FFRCT Planner’s luminal dimensions was assessed by using post-PCI optical coherence tomography as the reference. ResultsOverall, 259 patients were screened, with 120 patients (123 vessels) included in the final analysis. The mean patient age was 64 ± 9 years, and 24% had diabetes. Measured FFR post-PCI was 0.88 ± 0.06, and the FFRCT Planner FFR was 0.86 ± 0.06 (mean difference: 0.02 ± 0.07 FFR unit; limits of agreement: –0.12 to 0.15). Optical coherence tomography minimal stent area was 5.60 ± 2.01 mm2, and FFRCT Planner minimal stent area was 5.0 ± 2.2 mm2 (mean difference: 0.66 ± 1.21 mm2; limits of agreement: –1.7 to 3.0). The accuracy and precision of the FFRCT Planner remained high in cases with focal and diffuse disease and with low and high calcium burden. ConclusionsThe FFRCT-based technology was accurate and precise for predicting FFR after PCI. (Precise Percutaneous Coronary Intervention Plan Study [P3]; NCT03782688)

Differential Prognostic Implications of Pre- and Post-Stent Fractional Flow Reserve in Patients Undergoing Percutaneous Coronary Intervention.

The influence of pre-intervention coronary physiologic status on outcomes post percutaneous coronary intervention (PCI) is not well known. We sought to investigate the prognostic implications of pre-PCI fractional flow reserve (FFR) combined with post-PCI FFR. A total of 1,479 PCI patients with pre-and post-PCI FFR data were analyzed. The patients were classified according to the median values of pre-PCI FFR (0.71) and post-PCI FFR (0.88). The primary outcome was target vessel failure (TVF) at 2 years. The risk of TVF was higher in the low pre-PCI FFR group than in the high pre-PCI FFR group (hazard ratio, 1.82; 95% confidence interval, 1.15-2.87; p=0.011). In 4 group comparisons, the cumulative incidences of TVF at 2 years were 3.8%, 4.1%, 4.8%, and 10.2% in the high pre-/high post-, low pre-/high post-, high pre-/low post-, and low pre-/low post-PCI FFR groups, respectively. The risk of TVF was the highest in the low pre-/low post-PCI FFR group among the groups (p values for comparisons <0.05). In addition, the high pre-/low post-PCI FFR group presented a comparable risk of TVF with the high post-PCI FFR groups (p values for comparison >0.05). When the prognostic value of the post-PCI FFR was evaluated according to the pre-PCI FFR, the risk of TVF significantly decreased with an increase in post-PCI FFR in the low pre-PCI FFR group, but not in the high pre-PCI FFR group. Pre-PCI FFR was associated with clinical outcomes after PCI, and the prognostic value of post-PCI FFR differed according to the pre-PCI FFR. ClinicalTrials.gov Identifier: NCT04012281.

Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses

The aim of this study was to assess clinical outcomes after combined pressure and flow assessment of coronary lesions. Although fractional flow reserve (FFR) remains the invasive reference standard for revascularization, approximately 40% of stenoses have discordant coronary flow reserve (CFR). Optimal treatment for these disagreements remains unclear. A total of 455 subjects with 668 lesions were enrolled from 12 sites in 6 countries. Only lesions with reduced FFR and CFR underwent revascularization; all other combinations received initial medical therapy. Fourteen percent of lesions had FFR≤0.8 but CFR≥2.0 while 23% of lesions had FFR >0.8 but CFR<2.0. During 2-year follow-up, the primary endpoint of composite all-cause death, myocardial infarction, and revascularization in lesions with FFR≤0.8 but CFR≥2.0 (10.8% event rate) compared with lesions with FFR >0.8 and CFR≥2.0 (6.2% event rate) exceeded the prespecified+10% noninferiority margin (P=0.090). Target vessel failure models using both continuous FFR and continuous CFR found that only higher FFR was associated with reduced target vessel failure (Cox P=0.007) after initial medical treatment. Central core laboratory review accepted 69.8% of all tracings with mean differences of<0.01 for FFR and<0.02 for CFR, indicating no material impact on clinical measurements or outcomes. All-cause death, myocardial infarction, and revascularization after 2 years was not noninferior between lesions with FFR≤0.8 but CFR≥2.0 and lesions with FFR >0.8 and CFR≥2.0. These results do not support using invasive CFR≥2.0 to defer revascularization for lesions with reduced FFR if the patient would otherwise be a candidate on the basis of the entire clinical scenario and treatment preference.

Predictors and 3-year outcomes of compromised left circumflex coronary artery after left main crossover stenting.

BackgroundThere are few predictors of decreased fractional flow reserve (FFR) in the left circumflex coronary artery (LCx) after left main (LM) crossover stenting.ObjectivesWe aimed to determine the predictors for low FFR at LCx and possible treatment strategies for compromised LCx, together with their long‐term outcomes.MethodsAltogether, 563 patients who met the inclusion criteria were admitted to our hospital from February 2015 to November 2020 with significant distal LM bifurcation lesions. They underwent single‐stent crossover percutaneous coronary intervention (PCI) under intravascular ultrasound (IVUS) guidance with further LCx intervention based on the measured FFR.ResultsThe patients showed significant angiographic LCx ostial affection post‐LM stenting, but only 116 (20.6%) patients had FFR < 0.8. The three‐year composite major adverse cardiac events (MACE) rates were comparable between the high and low FFR groups (16.8% vs. 15.5; p = 0.744). In a multivariate analysis, low FFR at the LCx was associated with post‐stenting minimal luminal area (MLA) of LCx (odds ratio [OR]: 0.032, p < .001), post‐stenting LCx plaque burden (OR: 1.166, p < .001), poststenting LM MLA (OR: 0.821, p = .038), and prestenting LCx MLA (OR: 0.371, p = .044). In the low FFR group, those with compromised LCx managed with drug‐eluting balloon had the lowest three‐year MACE rate (8.1%), as compared to either those undergoing kissing balloon inflation (KBI) (17.5%) or stenting (20.5%) (p = 0.299).ConclusionUnnecessary LCx interventions can be avoided with FFR‐guided LCx intervention. Poststenting MLA and plaque burden of the LCx, and main vessel stent length are poststenting predictors of low FFR.

Prognostic Implications of Comprehensive Whole Vessel Plaque Quantification Using Coronary Computed Tomography Angiography.

The prognostic value of whole vessel plaque quantification has not been fully understood. We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed tomography angiography. In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area<4mm2, plaque burden≥70%, low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign; and high-risk vessel characteristics (HRVC) included total plaque volume≥306.5 mm3, fibrofatty and necrotic core volume≥4.46 mm3, or percent total atheroma volume≥32.2% in a target vessel, based on corresponding optimal cutoff values. Survival analysis for vessel-oriented composite outcome (VOCO) (a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization) at 5 years was performed using marginal Cox proportional hazard models. Whole vessel plaque quantification had incremental predictability in addition to % diameter stenosis and HRPC (P< 0.001) in predicting FFR≤0.80. Among 517 deferred vessels based on FFR >0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95%CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P< 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not. Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163).

Effects of salvianolate on microcirculatory disturbance in patients with stable coronary heart disease: study protocol for a randomized controlled trial

BackgroundObstruction of coronary microcirculation can lead to myocardial ischemia and poor prognosis. Salvianolate exerts cardiovascular protection at cellular levels. However, no studies have confirmed the effect of salvianolate on stable coronary heart disease (CHD) with high fractional flow reserve (FFR) and myocardial microcirculatory disturbances.Methods/designThis study will enroll 78 patients who have stable coronary disease with 50 to 70% stenosis in major coronary arteries and whose FFR > 0.80 and index of microcirculatory resistance (IMR) > 25. Patients will be randomly divided into the salvianolate group or the placebo group. After above evaluations, salvianolate 200 mg will be intravenously dripped immediately for the next 30 min and subsequent 7 days in the salvianolate group, and matching 0.9% normal saline will be arranged in the placebo group. IMR will be reevaluated in immediate phase after first 30 min of salvianolate or placebo treatment. The primary end point will be the IMR change in this phase, and the secondary end points will be the total ischemic burden assessed by the Seattle angina scale, quality of life scale, Holter electrocardiography, and 6-min walk test after 7 days before discharge.DiscussionThis study will firstly clarify the improvement effect of salvianolate on coronary microcirculation and provide an effective treatment method for stable CHD patients with high FFR and myocardial microcirculatory disturbance.Trial registrationChinese Clinical Trial Registry ChiCTR1800018772. Registered on 9 October 2018 and updated on 2 March 2020

The Hemodynamic Mechanism of FFR-Guided Coronary Artery Bypass Grafting.

Clinically, fractional flow reserve (FFR)-guided coronary artery bypass grafting (CABG) is more effective than CABG guided by coronary angiography alone. However, no scholars have explained the mechanism from the perspective of hemodynamics. Two patients were clinically selected; their angiography showed 70% coronary stenosis, and the FFRs were 0.7 (patient 1) and 0.95 (patient 2). The FFR non-invasive computational model of the two patients was constructed by a 0–3D coupled multiscaled model, in order to verify that the model can accurately calculate the FFR results. Virtual bypass surgery was performed on these two stenoses, and a CABG multiscaled model was constructed. The flow rate of the graft and the stenosis coronary artery, as well as the wall shear stress (WSS) and the oscillatory shear index (OSI) in the graft were calculated. The non-invasive calculation results of FFR are 0.67 and 0.91, which are close to the clinical results, which proves that our model is accurate. According to the CABG model, the flow ratios of the stenosis coronary artery to the graft of patient 1 and patient 2 were 0.12 and 0.42, respectively. The time-average wall shear stress (TAWSS) results of patient 1 and patient 2 grafts were 2.09 and 2.16 Pa, respectively, and WSS showed uniform distribution on the grafts. The OSI results of patients 1 and 2 grafts were 0.0375 and 0.1264, respectively, and a significantly high OSI region appeared at the anastomosis of patient 2. The FFR value of the stenosis should be considered when performing bypass surgery. When the stenosis of high FFR values is grafted, a high OSI region is created at the graft, especially at the anastomosis. In the long term, this can cause anastomotic blockage and graft failure.

Independent predictors of discordance between the resting full-cycle ratio and fractional flow reserve.

The resting full-cycle ratio (RFR), a novel resting index, is well correlated with and shows good diagnostic accuracy to the fractional flow reserve (FFR). However, discordance results between the RFR and FFR have been observed to occur in about 20% of cases. This study aimed to clarify the prevalence and factors of discordant results between the RFR and FFR through a direct comparison of these values in daily clinical practice. A total of 220 intermediate coronary lesions of 156 consecutive patients with RFR and FFR measurements were allocated to four groups according to RFR and FFR cutoff values. We compared the angiographic, clinical, and hemodynamic variables among the groups. Discordant results between the RFR and FFR were observed in 19.6% of vessels, and the proportion of discordant results was significantly higher in the left main trunk and left anterior descending artery (LM + LAD) than in non-LAD vessels (25.2% vs. 12.3%, p = 0.006). In the multivariable regression analysis, LM + LAD location, hemodialysis, and peripheral artery disease were associated with a low RFR among patients with a high FFR. Conversely, the absence of diabetes mellitus and the presence of higher hemoglobin levels were associated with a higher RFR among patients with a low FFR. Specific angiographic and clinical characteristics such as LM + LAD location, hemodialysis, peripheral artery disease, and absence of diabetes mellitus and anemia can be independent predictors of physiologic discordance between the RFR and FFR.

Fractional flow reserve and instantaneous wave-free ratio discordance in patients with severe aortic valve stenosis

Abstract Background It has been reported that discordance between fractional flow reserve (FFR) and Instantaneous Wave-Free Ratio (iFR) could occur in up to 20% of cases. However, there are no reports regarding discordance between FFR and iFR in patients with severe aortic valve stenosis (AS). Purpose We aimed to investigate the discordance between FFR and iFR in patients with severe AS. Methods Severe AS was defined as an aortic-valve area of ≤1.0 cm2, a mean aortic-valve gradient of 40mmHg or more, or a peak aortic-jet velocity of 4.0 m/s or more. Intermediate coronary artery stenosis was defined as 30% to 70% stenosis (visual estimation). FFR and iFR were calculated in 4 quadrants based on values of FFR ≤0.8 and iFR ≤0.89 (positive discordance; low FFR and high iFR, negative discordance; high FFR and low iFR). Results We examined consecutive 140 patients (164 intermediate coronary artery stenosis vessels). Mean FFR and iFR ± standard deviation was 0.82±0.09 and 0.82±0.14, respectively. The discordance was observed in 48 vessels (29.3%). In the discordant group, most of cases were negative discordance (45 cases, 93.6%). Binary logistic regression analysis showed that left anterior descending artery (Hazard Ratio 3.80; 1.55 to 9.31, p=0.0036) was independently associated with negative discordance. Conclusions In patients with severe AS, the discordance between FFR and iFR could be observed in 29.3% of the vessels, mostly negative discordance. The left anterior descending artery is an independent predictor for negative discordance. Funding Acknowledgement Type of funding source: None

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy. 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10-4 M, 81 mcg over 3minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBFACH ). Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBFACH ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBFACH change ≤50%. CFR modestly correlated with HMR (r=-0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p=.02), higher FFR (p=.03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina. In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.

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

Background and ObjectivesRecent 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.MethodsA 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.ResultsPatients 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).ConclusionAmong 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 RegistrationClinicalTrials.gov Identifier: NCT03690713