Positive Fractional Flow Reserve Research Articles

Discordance between quantitative coronary angiography and fractional flow reserve or intravascular ultrasound: a substudy of the FLAVOUR trial

Abstract Background Discrepancies between quantitative coronary angiography (QCA) and fractional flow reserve (FFR) or intravascular ultrasound (IVUS) are often observed in coronary lesions with intermediate stenosis. Objectives We investigated the impact of physiology- or intracoronary imaging-directed revascularization strategies on clinical outcomes in patients with discordant coronary lesions between QCA and FFR or IVUS. Methods This study was a post hoc analysis of the FLAVOUR study, an investigator-initiated, prospective, randomized, open-label, multinational trial performed at 18 sites in Korea and China. In the FLAVOUR study, 200 patients with ≥60% diameter stenosis (DS) deferred percutaneous coronary intervention (PCI) according to FFR > 0.8 (n=141) or a minimal lumen area > 3 mm2 or 3-4 mm2 with a plaque burden <70% on IVUS whereas 351 patients with <60% DS performed PCI according to positive FFR (n=118) or positive IVUS (n=233) results. The primary outcome was a patient-oriented composite outcome (POCO), a composite of death, myocardial infarction, or revascularization. Results The incidence of discordance was 28.1% in the FFR group and 32.4% in the IVUS group. At 24 months, among patients with ≥60% DS, the incidence of POCO was similar between FFR-guided and IVUS-guided deferral strategies (4.4% vs. 3.4%, p=0.757). Among patients with <60% DS, FFR-directed or IVUS-directed PCI did not differ in the POCO incidence (5.2% vs. 2.6%, p=0.207). However, FFR-guided PCI showed a higher incidence of periprocedural myocardial infarction than IVUS-guided PCI in <60% DS lesions (2.6% vs. 0.0%, p=0.014). Conclusions In patients with discordant intermediate stenosis between QCA and FFR or IVUS, physiology- and imaging-directed revascularization strategies are comparable concerning POCO at 24 months.

The Impact of Age on the Physiological Assessment of Borderline Coronary Stenoses.

Background and Objectives: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through ischemia assessment via one of the recommended methods of invasive evaluation. This study aimed to assess whether clinical factors influence the risk of a positive result in invasive myocardial ischemia assessment and if these potential factors change with the patient's age and the consistency of ischemia assessment. Materials and Methods: Data were collected retrospectively on all consecutive patients hospitalized in the University Hospital in Krakow between 2020 and 2021, on whom physiological assessments of coronary circulation were performed. Patients were divided into two groups: patients aged 60 or younger and patients older than 60. Results: Despite the older patients having more risk factors for CAD, their physiological assessment results of borderline lesions were similar to those of the younger patients. Positive fractional flow reserve (FFR) assessments were obtained from almost 50% of vessels. In the younger patients, cigarette use and type 2 diabetes mellitus increased the risk of a positive FFR result by 3.5 and 2.5 times, respectively. In the older patients, male gender and peripheral vascular disease significantly increased the risk of a positive FFR by 2.5 and 2 times, respectively. Conclusions: Clinical characteristics of patients undergoing physiological assessment of borderline coronary stenosis varied significantly by age. Refining the definition of borderline lesions to include age, gender, and other factors may improve the identification of patients who would benefit from physiological assessment and coronary revascularization.

Influence of sex on the functional assessment of myocardial ischemia.

Fractional flow reserve (FFR) and non-hyperemic resting pressure ratios, such as instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR), are recommended for evaluating the significance of angiographically intermediate coronary stenoses. Despite their usefulness, approximately 20% of assessed lesions exhibit discordance between FFR and iFR/RFR. The role of sex in this discrepancy remains uncertain; thus, we aimed to investigate its impact on the discordance between FFR and iFR/RFR. We reviewed 417 consecutive intermediate stenotic lesions from 381 patients, stratified by sex and assessed with both FFR and iFR/RFR. FFR≤0.80 and iFR/RFR ≤0.89 were considered positive for ischemia. Among the 381 patients, 92 (24.1%) were women. Women were older, had lower estimated glomerular filtration rate (eGFR), a higher ejection fraction, and were more likely to have peripheral artery disease than men. Median FFR and iFR/RFR values were lower in men than in women (FFR 0.86 vs. 0.80; P < 0.001; iFR 0.92 vs. 0.90; P = 0.049). However, overall discordance prevalence was similar for both sexes (20.6% vs. 15.1%; P = 0.22). In men, eGFR, insulin-treated diabetes mellitus, and arterial hypertension were predictors of positive FFR | negative iFR/RFR discordance, while eGFR, insulin-treated diabetes mellitus, atrial fibrillation, and chronic obstructive pulmonary disease were predictors of negative FFR | positive iFR/RFR discordance. No factors associated with either discordance were identified in women. FFR and iFR/RFR results indicating significant ischemia were more common in men than women when assessing intermediate coronary stenoses. Nevertheless, sex did not predict discordant results.

Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.

To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography. We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (n = 14) and texture (n = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images. Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%. In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.

Vessel-Specific Outcomes of Deferred Revascularization Following Negative Fractional Flow Reserve

Variations in myocardial supply area and hydrostatic pressure gradients result in greater likelihood of positive fractional flow reserve (FFR) in the left anterior descending (LAD) compared with the circumflex (Cx) and right coronary artery (RCA). However, the same FFR threshold for deferral of revascularization is applied to all arteries, without evidence that this results in equivalent outcomes. We assessed vessel-specific outcomes of deferred revascularization for the 3 major coronary arteries based on FFR > 0.8. In this retrospective study, data were obtained on consecutive patients who underwent indicated FFR assessment across 2 tertiary institutions. Patients with deferred revascularization were followed for 36 months for the primary end point of vessel-specific target lesion failure (TLF). Of 1,916 major coronary arteries (1,579 patients), the odds ratio of positive FFR was highest in the LAD (odds ratio 3.36, p<0.001). In total, 867 vessels (733 patients) with FFR > 0.8 had complete 3-year medical record follow-ups. The TLF rate for deferred vessels was 10.21%, 11.52%, and 10.96% for the LAD, Cx, and RCA respectively. In a multivariate analysis, there was no significant difference in the odds of TLF for the 0.84 (0.53 to 1.33, p=0.459), 1.17 (0.68 to 2.01, p=0.582), and 1.11 (0.62 to 2.00, p=0.715) in the LAD, Cx, and RCA, respectively. In a multivariate analysis, diabetes mellitus was the only baseline characteristic significantly associated at risk of TLF (1.43 [1.01 to 2.02], p=0.043). In conclusion, despite greater likelihood of positive FFR in the LAD, the FFR threshold for deferred revascularization resulted in equivalent outcomes in all 3 major coronary arteries, and patients with diabetes mellitus may represent a group that requires aggressive surveillance and risk factor modification after deferred revascularization.

Discrepancy between plaque vulnerability and functional severity of angiographically intermediate coronary artery lesions.

This study sought to investigate the relationship between physiological severity and plaque vulnerability of intermediate coronary artery stenoses as assessed by fractional flow reserve (FFR) and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We included vessels where both FFR and NIRS-IVUS were performed. A positive FFR was defined as FFR ≤ 0.80. Lipid core burden index of the entire target vessel (TV-LCBI), maximum LCBI in 4mm (maxLCBI4mm), and maximum plaque burden (PB) were evaluated using NIRS-IVUS. A vulnerable plaque was defined as a lipid-rich plaque (maxLCBI4mm ≥ 400) with large PB (≥ 70%). A total of 59 vessels of 45 patients were included. Median FFR value was 0.75 [interquartile 0.72, 0.82]. An FFR value of ≤ 0.80 was observed in 42 vessels (71%). TV-LCBI (correlation coefficient [CC] = -0.331, p = 0.011), lesion length (CC = -0.350, p = 0.007), and PB (CC = -0.230, p = 0.080) negatively correlated with FFR value, while maxLCBI4mm did not (CC = -0.156, p = 0.24). The prevalence of vulnerable plaques (26.2% vs. 29.4%, p > 0.99) and mean TV-LCBI, maxLCBI4mm, and PB values were not significantly different between the vessels with FFR ≤ 0.80 and those with FFR > 0.80. In multivariable logistic models, diabetes mellitus (p = 0.003) and hemoglobin A1c (p = 0.012) were associated with the presence of a vulnerable plaque. In conclusion,the results of the present study suggested that FFR may reflect total lipid burden but not necessarily plaque vulnerability. In patients with coronary artery disease and a high likelihood of rapid atherosclerosis progression, such as diabetes mellitus patients, assessing plaque vulnerability in addition to the functional severity of coronary artery lesions may help stratify better the risk of future events.

Factors associated with discordance between fractional flow reserve and resting full-cycle ratio

BackgroundResting full-cycle ratio (RFR), a non-hyperemic pressure ratio, is alternative to fractional flow reserve (FFR) for the evaluation of coronary artery stenoses. Although FFR and RFR results are often discordant using the cut-off values (0.80 and 0.89), factors associated with the discordance are unclear. The aim of this study was to explore factors related to the discordant results. MethodsWe performed FFR and RFR measurements in a total of 408 vessels with intermediate coronary artery stenosis in 277 patients. Positive FFR and RFR were defined based on the cut-off values of 0.80 and 0.89. The discordance was determined as positive FFR and negative RFR (FFR ≤0.80 and RFR >0.89) or negative FFR and positive RFR (FFR >0.80 and RFR ≤0.89). ResultsOverall, FFR and RFR were significantly correlated (r = 0.76, p < 0.001), while positive FFR and negative RFR and negative FFR and positive RFR were observed in 44 (10.8%) and 45 (11.0%) of 408 vessels, respectively. Smaller body surface area, diabetes, chronic kidney disease including hemodialysis, severe aortic stenosis, higher E/e', and lower left ventricular ejection fraction on echocardiography, and lower hemoglobin and higher brain natriuretic peptide levels were identified as factors associated with the negative FFR and positive RFR discordance. ConclusionsDiscordant results between FFR and RFR were often found in more than 20% of vessels with intermediate coronary stenosis. Clinical characteristics such as renal function, heart failure, and anemia may be considered in clinical decision-making when using FFR and RFR.

Prevalence of myocardial perfusion scintigraphy derived ischemia in coronary lesions with discordant fractional flow reserve and non-hyperemic pressure ratios

BackgroundWhether a coronary lesion with discordant fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) causes myocardial ischemia remains unclear. This study investigates the prevalence of myocardial ischemia as assessed by myocardial perfusion scintigraphy (MPS) in coronary lesions with discordant FFR and instantaneous wave-free ratio (iFR), and, additionally, other NHPRs: resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and resting Pd/Pa. MethodsA total of 484 coronary arteries in 295 patients with stable coronary artery disease that underwent MPS and invasive physiological pressure measurements were categorized into four groups (FFR+/NHPR+, FFR+/NHPR-, FFR-/NHPR+, and FFR-/NHPR-) using the respective cut-off values of FFR ≤ 0.80, iFR ≤ 0.89, RFR ≤ 0.89, dPR < 0.89, and Pd/Pa ≤ 0.92. The proportions of MPS-derived myocardial ischemia in a relevant myocardial territory were compared between the four groups. ResultsIn total, 175 (36%), 61(13%), 35(7%) and 213(44%) vessels were classified into FFR+/iFR+, FFR+/iFR-, FFR-/iFR+ and FFR-/iFR- groups, respectively. The FFR+/iFR+ group had the highest proportion of MPS-derived ischemia (70%), followed by the FFR+/iFR- group (38%), the FFR-/iFR+ group (23%), and the FFR-/iFR- group (10%) (P < 0.001). Similar proportions of MPS-derived ischemia were found when RFR.(70%, 34%, 24%, and 10%, P < 0.001), dPR (70%, 38%, 26%, and 10%, P < 0.001), and Pd/Pa (70%, 31%, 22%, and 10%, P < 0.001) were used in place of iFR. ConclusionsThe prevalence of MPS-derived myocardial ischemia in coronary lesions with discordance between FFR and NHPRs is lower than those with concordantly positive FFR and NHPRs, but higher than those with concordantly negative FFR and NHPRs.

Efficacy of fractional flow reserve measurement in the assessment of stenotic lesions of coronary artery

Context: The decision to perform an intervention on a narrowed coronary artery depends on the ischemia caused by the stenosis. The indication for intervention usually applies to cases with ≥70% stenosis of vascular diameter because of the risk of myocardial ischemia. Aims: To define the efficacy of fractional flow reserve (FFR) measurement in the evaluation of coronary artery stenosis. Methods: This prospective study was conducted on patients with intermediate coronary artery stenosis who underwent quantitative coronary angiography after coronary computed tomography angiography. Results: The study population consisted of 46 men and 26 women with a mean age of 66.0 ± 12.9 years. FFR was significantly correlated with the grade of angina pectoris (r = – 0.387; p&lt;0.01) and showed a negative correlation with percentage diameter stenosis (r = – 0.241, p&lt;0.05) and a positive correlation with the minimal lumen diameter (MLD; r = 0.377, p&lt;0.05). The cut-off value to predict positive FFR was &gt;55.62% diameter stenosis and MLD ≤ 1.08 mm. FFR ≤ 0.80 indicating intervention and FFR &gt; 0.80 indicating medical therapy were observed in 56.9% and 43.1% of the cases, respectively. No major cardiac complications occurred during 12 months of follow-up in both groups. Conclusions: FFR measurements for intermediate stenosis of the coronary artery should be used to evaluate the possibility of myocardial ischaemia. If FFR is not available, a cut-off point of &gt;55.62% diameter stenosis or MLD ≤ 1.08 mm can be used to predict the FFR results.

Association of coronary perivascular fat attenuation index, the parameters of plaque and fractional flow reserve

Objective: To explore the association of coronary perivascular fat attenuation index (FAI), the parameters of plaque and fractional flow reserve (FFR). Methods: A total of 113 patients (with 141 plaques) (78 males and 35 females, age from 40 to 83 years) with stable coronary artery disease were retrospectively collected from Jingling Hospital and Shanghai Sixth People's Hospital. All the patients underwent coronary CT angiography and invasive FFR examinations. The quantitative and qualitative parameters of plaque and vessel (such as the length and volume of plaque, the characteristics of plaque and high-risk plaque) and the FAI around the plaque were measured. The patients were divided into positive FAI group (n=46) and negative FAI group (n=66) according to the standard of whether the threshold of FAI≥ -70 HU. The quantitative indexes, including age, the length and volume of plaque, minimal lumen area (MLA) and FAI, as well as the qualitative indexed, including the characteristics of plaque, the number and characteristic of high-risk plaque and the number of patients and plaque with positive FFR were compared between the two groups. Further, logistic regression analysis was performed to analyze the correlation among myocardial ischemia, age, the length of plaque, minimal lumen area (MLA), FAI and so on. ROC curve was used for evaluating the performance of each parameter. Results: Compared to the negative FAI group, positive FAI group had lower MLA (2.00±1.33 mm2 vs 4.13±2.41 mm2, P<0.001). The proportion of patients and vessels with FFR<0.75 in positive FAI group were significantly higher than that in negative FAI group (21.3% vs 4.5%, P=0.006; 23.2% vs 8.2%, P=0.016). The FAI between high-risk plaque and non-high-risk plaque had no significant difference (21.2% vs 16.1%, P=0.451). FAI predicted myocardial ischemia (AUC=0.666, P=0.021) and significantly improved the prediction efficiency of complex model(0.915 vs 0.951,P=0.033). Conclusion: Lower MLA and higher incidence of myocardial ischemia were associated with patients with higher FAI. In addition, FAI has a certain prediction efficiency and can provide incremental value for the determination of myocardial ischemia.

Stress Myocardial Perfusion Imaging Interpretation From the Viewpoint of Fractional Flow Reserve.

Myocardial perfusion imaging (MPI) and fractional flow reserve (FFR) are established approaches to the assessment of myocardial ischemia. Recently, various FFR cutoff values were proposed, but the diagnostic accuracy of MPI in identifying positive FFR using various cutoff values is not well established.Methods and Results:We retrospectively studied 273 patients who underwent stress MPI and FFR within a 3-month period. Results for FFR were obtained from 218 left anterior descending artery (LAD) lesions and 207 non-LAD lesions. Stress MPI and FFR demonstrated a good correlation in the detection of myocardial ischemia. However, the positive predictive value (PPV) of FFR for detecting MPI-positive lesions at the optimal FFR thresholds was insufficient (44% for LAD and 65% for non-LAD lesions). This was caused by a sharp drop in PPV at an FFR threshold of 0.7 or more. Notably, 41% of the lesions with normal MPI demonstrated FFRs <0.80. However, MPI-negative lesions had an extremely low lesion rate with FFR <0.65 (6%). Conversely, 78% and 41% of MPI-positive lesions had FFR <0.80 and <0.65, respectively. The data confirmed that decisions based on MPI are reasonable because MPI-negative patients have an extremely low rate of lesions with a FFR below the cutoff point for a hard event, and MPI-positive lesions include many lesions with FFR <0.65.

Discordant resting and hyperaemic coronary physiology among unselected patients referred for coronary angiography: a single centre experience

Abstract Background Physiological assessment of intermediate coronary artery lesions to guide therapy is well established. Recently, the use of non-hyperaemic pressure ratios (NHPRs) has been suggested as a reliable alternative to hyperaemic assessment, such as fractional flow reserve (FFR). However certain patient / lesion subsets, including proximal lesion location, young patient age and assessment of non-LAD vessels, have been associated with discordance of resting and hyperaemic measurements which has led to some confusion over their interpretation and integration into routine clinical practice. Purpose To evaluate the frequency of discordant resting and hyperaemic measurements among patients undergoing assessment of intermediate coronary artery stenoses, and to identify common lesion-specific features within patients with discordant data. Methods From our coronary physiology database, we identified consecutive lesions which had been assessed between October 2020 and March 2021 with both resting (resting full-cycle ratio; RFR) and hyperaemic (wire-based FFR with peripheral adenosine) indices. Positive RFR defined as &amp;lt;0.89 (negative RFR &amp;gt;0.93, grey zone RFR 0.89–0.93). Positive FFR defined as &amp;lt;0.80 (negative FFR ≥0.80). Concordance between measurements was assessed: Group 1 (RFR -ve, FFR +ve: positive discordance); Group 2 (RFR -ve, FFR -ve: normal concordance), Group 3 (RFR +ve, FFR +ve: abnormal concordance) and Group 4 (RFR +ve, FFR -ve: negative discordance). Results 100 lesions were identified as being assessed with both RFR and FFR, in 83 patients (67% male), mean age 67 (±12) years, vessel assessed; LAD 66, RCA 19, LCx 13, LMCA 1 and radial graft 1; with 45 being proximal lesions. 30 RFR measurements were in the grey zone. Of the remaining 70 lesions, 55 results (79%) were concordant (Group 2 = 31, Group 3 = 24), with 15 results (21%) being discordant (Group 1 = 3, Group 4 = 12). Negative predictive value (NPV) of RFR (for FFR &amp;lt;0.80) was 91%, when grey zone RFR measurements were excluded. Discordance was not related to age (69 vs 68 years, p=0.75), lesion location (proximal lesion with discordance (6/15) vs proximal lesion with concordance (27/55), p=0.91, figure 1) or non-LAD vessel (non-LAD with discordance (9/15) vs non-LAD lesion with concordance (20/55), p=0.77, figure 2). Conclusion Overall within our patient group, there appeared to be a good association of RFR to FFR. In particular, RFR had a high NPV for an FFR &amp;lt;0.80. The clinical relevance of discordant measurements requires further investigation. However, our data suggest that a positive RFR (&amp;lt;0.89) measurement may not always correlate with a significant FFR measurement (&amp;lt;0.80), and the mechanism for this is unclear. Consequently, caution should be applied when including these measures in every day practice, in particular within patients with a positive RFR measurement. Funding Acknowledgement Type of funding sources: None.

Ischemia From Nonculprit Stenoses Is Not Associated With Reduced Culprit Infarct Size in Patients with ST-Segment-Elevation Myocardial Infarction.

In patients with ST-segment-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention, reperfusion injury accounts for a significant fraction of the final infarct size, which is directly related to patient prognosis. In animal studies, brief periods of ischemia in noninfarct-related (nonculprit) coronary arteries protect the culprit myocardium via remote ischemic preconditioning. Positive fractional flow reserve (FFR) documents functional significant coronary nonculprit stenosis, which may offer remote ischemic preconditioning of the culprit myocardium. The aim of the study was to investigate the association between functional significant, multivessel disease (MVD) and reduced culprit final infarct size or increased myocardial salvage (myocardial salvage index [MSI]) in a large contemporary cohort of STEMI patients. Cardiac magnetic resonance was performed in 610 patients with STEMI at day 1 and 3 months after primary percutaneous coronary intervention. Patients were stratified into 3 groups according to FFR measurements in nonculprit stenosis (if any): angiographic single vessel disease (SVD), FFR nonsignificant MVD (functional SVD), or FFR-significant, functional MVD. A total of 431 (71%) patients had SVD, 35 (6%) had functional SVD, and 144 (23%) had functional MVD. There was no difference in final infarct size (mean infarct size [%left ventricular mass] SVD, 9±3%; functional SVD, 9±3%; and functional MVD, 9±3% [P=0.82]) or in MSI between groups (mean MSI [%left] SVD, 66±23%; functional SVD, 68±19%; and functional MVD, 69±19% [P=0.62]). In multivariable analyses, functional MVD was not associated with larger MSI (P=0.56) or smaller infarct size (P=0.55). Functional MVD in nonculprit myocardium was not associated with reduced culprit final infarct size or increased MSI following STEMI. This is important knowledge for future studies examining a cardioprotective treatment in patients with STEMI, as a possible confounding effect of FFR-significant, functional MVD can be discarded. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

Anatomical-functional discordance between quantitative coronary angiography and diastolic pressure ratio during wave-free period.

This study sought to determine the predictors of anatomical-functional discordance between quantitative coronary angiography (QCA) derived diameter stenosis (QCA-DS) and diastolic pressure ratio during wave-free period (dPRWFP ). The discrepancy between angiographical stenosis and physiological significance is frequently experienced in clinical practice. Although the anatomical-functional discordance between angiography and fractional flow reserve (FFR) has been intensively investigated, that of resting index including dPRWFP remains to be elucidated. In a total of 647 angiographically intermediate lesions with QCA-DS between 30 and 70% in 502 patients, predictors of having QCA-DS >50% and dPRWFP > 0.89 (QCA-dPRWFP mismatch), and those of having QCA-DS ≤50% and dPRWFP ≤ 0.89 (QCA-dPRWFP reverse mismatch) were determined. FFR ≤0.80 was defined as positive FFR and the predictors of QCA-FFR discordance were determined as well. QCA-dPRWFP mismatch and reverse mismatch were observed in 27.5 and 17.6% of cases, respectively. The predictors of mismatch were non-left anterior descending artery (LAD) lesion, large minimal lumen diameter, low baseline heart rate, and high coronary flow reserve (CFR), while those of reverse mismatch were LAD lesion, non-culprit lesion of acute coronary syndrome, long lesion length, low left ventricular ejection fraction, and low CFR and index of microcirculatory resistance. Age, sex, and the culprit vessel of prior myocardial infarction were not significant determinants of QCA-dPRWFP discordance unlike QCA-FFR discordance derived from the same cohort. Anatomical-functional discordance between angiography and dPRWFP was not uncommon. Predictors differed between QCA-dPRWFP discordance and QCA-FFR discordance.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 μg, with dose doubling at each step). We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Usefulness of Fractional Flow Reserve during Routine Clinical Procedures in All-Comer Coronary Artery Disease Patients

Background: Fractional flow reserve (FFR)-guided interventions, though proved to be safe, continue to be a much-underutilized modality in determining treatment strategy, and data is lacking in Indian population. Objective: We aimed to determine the use of FFR-guided PCI and assess the overall impact on treatment decisions and clinical outcomes in patients with acute coronary syndrome (ACS) or chronic coronary syndromes (CCS). Methods: In this single-center retrospective and prospective observational study, FFR had been performed for the evaluation of treatment reclassification and clinical outcomes, as per physician’s clinical practice. Results: Data was obtained for 250 subjects (mean age 60.45 ± 9.6 years) with 324 lesions. The treatment plan based on angiography alone changed in 28% of lesions post-hyperemic FFR. The initial treatment plan based on angiography vs. the final treatment plan post-FFR (>0.80) was medical management 56.5% vs. 66.0%; CABG 11.1% vs. 7.7%; and PCI 32.4% vs. 26.2%. In subjects initially assigned to medical management, 14% had changed to PCI, and for subjects initially assigned to PCI, 44% had changed to medical therapy. Receiver operating characteristics (ROC) curve analysis revealed a good correlation between a resting FFR value of Conclusion: This study supports the use of FFR in determining treatment strategy in ACS or CCS patients with low MACE. Resting FFR value of be an alternative to intracoronary nitroglycerine/adenosine/Nikorandil-induced FFR in predicting positive FFR particularly in hemodynamically unstable patients, and who are intolerant to hyperemic drugs.

Two-Year Outcomes of Asymptomatic vs. Symptomatic Patients After Deferral of Revascularization Based on Fractional Flow Reserve - Insights From the J-CONFIRM Registry.

Background: The effect of symptoms on clinical outcomes after deferral of revascularization based on fractional flow reserve (FFR) remains poorly understood.Methods and Results: From the J-CONFIRM (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter) Registry, this study evaluated 1,215 patients with stable coronary artery disease, including symptomatic and asymptomatic patients (n=571 and 644, respectively). The primary endpoint was the cumulative 2-year incidence of target vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). An inverse probability weighted analysis was performed to adjust for the differences in baseline clinical characteristics between the 2 groups. At 2 years, the TVF rate did not differ significantly between symptomatic and asymptomatic patients (6.5% vs. 4.9%, respectively; P=0.15) or between symptomatic and asymptomatic patients with lesions with an FFR ≤0.80 (8.0% vs. 12.3%, respectively; P=0.20). Conversely, symptomatic patients showed significantly higher rates of TVF (6.2% vs. 3.3%; P=0.01) and CDTVR (6.2% vs. 3.1%; P=0.009) than asymptomatic patients, regardless of negative FFR values (>0.80).Conclusions: Despite negative FFR values, symptomatic patients were at higher risk of TVF than asymptomatic patients, driven primarily by a higher rate of CDTVR. Conversely, those with a positive FFR were likely to develop TVF regardless of their symptoms.

Long-Term Clinical Outcomes of Nonhyperemic Pressure Ratios: Resting Full-Cycle Ratio, Diastolic Pressure Ratio, and Instantaneous Wave-Free Ratio.

BackgroundNonhyperemic pressure ratios (NHPRs) such as instantaneous wave‐free ratio, resting full‐cycle ratio, or diastolic pressure ratio have emerged as invasive physiologic indices precluding the need for hyperemic agents. The current study sought to evaluate the long‐term prognostic implications of NHPRs compared with fractional flow reserve (FFR).Methods and ResultsNHPRs were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The association between NHPRs and the risk of 5‐year vessel‐oriented composite outcomes (VOCO, a composite of cardiac death, vessel‐related myocardial infarction, and ischemia‐driven revascularization) were analyzed among 864 deferred vessels. Lesions with positive NHPRs (instantaneous wave free ratio, resting full‐cycle ratio, and diastolic pressure ratio ≤0.89) or FFR (≤0.80) showed significantly higher risk of VOCO at 5 years than those with negative NHPRs or FFR, respectively. Discriminant ability for 5‐year VOCO was not different among NHPRs and FFR (C‐index: 0.623–0.641, P for comparison=0.215). In comparison of VOCO among the groups with deferred concordant negative (NHPRs−/FFR−), deferred discordant (NHPRs+/FFR− or NHPRs−/FFR+), and revascularized vessels, the cumulative incidence of VOCO were 7.5%, 14.4%, and 14.8% (log‐rank P<0.001), respectively. The deferred discordant group showed similar risk of VOCO with the revascularized vessel group (hazard ratio, 0.981; 95% CI 0.434–2.217, P=0.964).ConclusionsCurrently available invasive pressure‐derived indices showed similar prognostic implications for vessel‐related events at 5 years. Deferred lesions with discordant results between NHPRs and FFR did not show higher risk of vessel‐related events at 5 years than revascularized vessels.RegistrationURL: https://www.clini​caltr​ials.gov; Unique identifiers: NCT01621438, NCT01621438.

Diagnostic performance of quantitative, semi-quantitative, and visual analysis of dynamic CT myocardial perfusion imaging: a validation study with invasive fractional flow reserve.

To investigate the diagnostic performance of absolute myocardial blood flow (MBF), MBFratio, and visual analysis of dynamic CT myocardial perfusion imaging (CT-MPI) for the detection of hemodynamically significant coronary stenosis. Consecutive patients with chest pain and intermediate-to-high pre-test probability of obstructive coronary artery disease were prospectively enrolled. All patients were referred for dynamic CT-MPI and fractional flow reserve (FFR) measurements within 4weeks. Absolute MBF, MBFratio (mean MBF of stenosis-subtended territories versus that of reference territories), and visually identified perfusion defect were tested for the diagnostic performance with reference to FFR. Sixty-two patients with 95 target vessels were included for final analysis. The mean radiation dose for dynamic CT-MPI was 3.0 (2.2-4.0) mSv. The mean lesion-based absolute MBF value was significantly lower in ischemic segments than that in non-ischemic segments (78.0 (65.0-86.0) mL/min/100mL vs. 133.0 (117.5-163.8) mL/min/100mL, p < 0.001). Similarly, the lesion-based MBFratio was also markedly lower in territories with positive FFR results (0.52 (0.44-0.64) vs. 0.93 (0.91-0.97), p < 0.001). According to per-lesion ROC curve analysis, MBF and MBFratio had a similar area under the curve (AUC) for detecting hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for MBF and 96.1%, 93.2%, and 94.7% for MBFratio. Absolute MBF and MBFratio had similarly excellent diagnostic performance with reference to FFR. In addition, these two parameters outperformed visual analysis for the detection of myocardial ischemia. • The mean MBF and MBFratio were significantly lower in ischemic segments than those in non-ischemic segments. • Absolute MBF and MBFratio had similar AUCs for the detection of hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). • The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for absolute MBF and 96.1%, 93.2%, and 94.7% for MBFratio.

Artificial intelligence approaches to predict coronary stenosis severity using non-invasive fractional flow reserve

Fractional flow reserve is the current reference standard in the assessment of the functional impact of a stenosis in coronary heart disease. In this study, three models of artificial intelligence of varying degrees of complexity were compared to fractional flow reserve measurements. The three models are the multivariate polynomial regression, which is a statistical method used primarily for correlation; the feed-forward neural network; and the long short-term memory, which is a type of recurrent neural network that is suited to modelling sequences. The models were initially trained using a virtual patient database that was generated from a validated one-dimensional physics-based model. The feed-forward neural network performed the best for all test cases considered, which were a single vessel case from a virtual patient database, a multi-vessel network from a virtual patient database, and 25 clinically invasive fractional flow reserve measurements from real patients. The feed-forward neural network model achieved around 99% diagnostic accuracy in both tests involving virtual patients, and a respectable 72% diagnostic accuracy when compared to the invasive fractional flow reserve measurements. The multivariate polynomial regression model performed well in the single vessel case, but struggled on network cases as the variation of input features was much larger. The long short-term memory performed well for the single vessel cases, but tended to have a bias towards a positive fractional flow reserve prediction for the virtual multi-vessel case, and for the patient cases. Overall, the feed-forward neural network shows promise in successfully predicting fractional flow reserve in real patients, and could be a viable option if trained using a large enough data set of real patients.