Changes In Fractional Flow Reserve Research Articles

Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices.

Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta-analysis was to study immediate and long-term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). Lesion-specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (-0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut-offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

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

Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Predictors of successful post-PCI optimization in vessels with post-PCI fractional flow reserve &amp;lt;0.90: findings from the FFR REACT trial

Abstract Introduction Recent studies demonstrated a strong relation between suboptimal post-PCI fractional flow reserve (FFR) and clinical outcome. The feasibility of post-PCI FFR optimization and its impact on future clinical outcome remains topic of debate. Purpose The aim of the present substudy of the FFR REACT trial was to identify predictors of 1) absolute FFR increase following optimization and 2) successful functional optimization (final FFR ≥0.90). Methods The FFR REACT trial was a single-center, investigator initiated, randomized controlled trial including patients with (un)stable angina or non-ST segment elevation myocardial infarction and angiographically successful PCI. Following a post-PCI FFR &amp;lt;0.90, patients were randomized to intravascular ultrasound (IVUS)-guided optimization according to a dedicated optimization protocol (intervention arm) or no further treatment (control arm). In case of PCI optimization, FFR and IVUS were repeated to evaluate the optimization result. The present analysis included all patients randomized to IVUS-guided optimization, who actually underwent PCI optimization, and who had pre- and post-optimization FFR values available. We performed multivariate linear and logistic regression models to identify predictors of absolute FFR increase and FFR ≥0.90 following optimization. Results A total of 145 patients were allocated to the IVUS-guided optimization arm with 152 vessels having a post-PCI FFR &amp;lt;0.90 (mean post-PCI FFR: 0.83±0.05), of which 104 vessels (68.4%) underwent additional treatment after IVUS evaluation. Paired FFR measurements (pre- and post-optimization) were available in 100/104 optimized vessels. The mean absolute change in FFR was 0.03±0.06 (p&amp;lt;0.001), and 20/100 (20%) vessels achieved a final FFR ≥0.90. Both left anterior descending arteries (LAD) (mean change = -0.033, 95%CI -0.055- -0.010, p=0.004) and higher post-PCI FFR values (mean change per 0.01 unit increase = -0.005, 95%CI -0.007 - -0.004, p&amp;lt;0.001) were associated with lower changes in FFR following optimization. Independent predictors of achieving a final FFR ≥0.90 were higher post-PCI FFR values (OR 1.26 per 0.01 unit increase, 95%CI 1.06-1.51, p=0.009) and non-LAD vessels (OR 5.72, 95%CI 1.73-18.94, p=0.004). Conclusions Within the FFR REACT trial, we observed that the likelihood of improvement in final FFR values was driven by the initial post-PCI FFR values (before optimization) and the location of the target vessel, with non-LAD lesion location being a significant predictor of FFR increase.

Effects of guiding catheter on franctional flow reserve and non-hyperemic pressure ratios for the assessment of coronary artery stenoses

Abstract Aims Non-hyperemic pressure-derived Indexes (NHPI) provide diagnostic efficacy equivalent to fractional flow reserve (FFR) to guide percutaneous coronary interventions. In the Disengage (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, selective decannulation of the guiding catheter (GC) within the coronary ostium during FFR assessment was associated with a significant overall decrease in FFR, particularly when the stenosis was located in the proximal and middle coronary segments. So far it is unclear what influence the selective cannulation of the catheter in the coronary artery ostium has on the NHPI. This prospective registry aimed to evaluate the influence of GC engagement within the coronary ostium on FFR and NHPI values. Methods and results In the DISENGAGE@Rest (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) 133 patients with 164 intermediate coronary artery stenoses (40-90%) were enrolled. We evaluated: 1) the impact of GC engagement within the coronary ostium on FFR and NHPI values; 2) implications for clinical decision making; 3) the relationship between coronary physiology indices and study site (proximal, middle and distal coronary segments). Disengagement of GC was associated with a significant decrease in FFR (FFReng, 0.85±0.07 vs. FFRdis, 0.83±0.07; p&amp;lt; .001), Pd/Pa (Pd/Paeng, 0.94±0.05 vs. Pd/Padis, 0.93±0.05; p&amp;lt; .001) and RFR values (RFReng, 0.91±0.07 vs. RFRdis, 0.90±0.07; p= .018). This significant decrease in invasive physiologic indexes was driven by a significant increase in mean Pa value (Pa eng, 93±15 mm Hg vs. Pa dis, 97±15 for FFR; P &amp;lt; .001; Pa eng, 94±15 mm Hg vs Pa dis, 96±15 for Pd/Pa; P &amp;lt; .001 Pa eng, 95±15 mm Hg vs Pa dis, 97±15 for RFR; P &amp;lt; .001), without changes in mean Pd value. In 24 (15%), 12 (7%) and 17 (10%) lesions, FFR, RFR and Pd/Pa values, respectively, shifted below the cut-off point after GC disengagement with changes in clinical decision-making. There was a significant FFR change, but no NHPI, across different segments (ΔFFReng–FFRdis proximal 0.04±0.03 vs. ΔFFReng–FFRdis middle 0.02±0.02 vs. ΔFFReng–FFRdis distal 0.03±0.04; p= .018). Conclusions The results confirm a significant overall decrease in FFR after GC disengagement and extend this to Pd/Pa and RFR. In case of proximal coronary artery disease, GC disengagement should be performed in order not to underestimate the hemodynamic significance of the lesion under examination.

The importance of baseline fractional flow reserve to detect significant coronary artery stenosis in different patient populations.

Fractional flow reserve (FFR) assessment compares the blood flow on either side of a blockage in the coronary artery and indicates how severe the stenosis is in the artery. Intravenous adenosine is widely used to achieve conditions of stable hyperaemia for the measurement of FR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Therefore, FFR has some limitations, such as the side effects of adenosine and the long procedure time. In addition, there are not enough studies on the evaluation of the baseline ratio of distal coronary pressure to aortic pressure (Pd/Pa) according to standard cut-off values in coronary stenosis under special clinical conditions. This study aimed to assess the diagnostic power of the baseline FFR value for critical coronary stenosis and to determine its predictive value in special patient groups. This retrospective study included 158 patients, who were stratified as Q1 (< 0.89), Q2 (0.89-0.92), Q3 (0.93-0.95) and Q4 (> 0.95) based on baseline FFR values. The baseline Pd/Pa value, the change in adenosine FFR and the raw FFR change were recorded. Its predictive value was also calculated for specific patient groups. The threshold value of baseline FFR level for predicting critical stenosis was ≤ 0.92 with a sensitivity of 92.8% and a specificity of 82% (upper limit of Q2 cartilage). Patients with a baseline FFR value ≤ 0.92 had a 58.4-fold greater likelihood of a critical outcome compared with patients with a baseline FFR value > 0.92 (OR: 58.4; 95% CI: 20.3-124.6). In patients with a baseline FFR ≤ 0.92, the Q1 group had a 10.23-fold higher odds of critical stenosis compared with the Q2 group (OR: 10.23; 95% CI: 2.14-48.84). The same values had similar diagnostic power for all specific patient groups. The baseline FFR value could be used to predict critical coronary stenosis in our patients and had similar value for predicting lesion severity in all the subgroups.

Identification of ischemia-causing lesions using coronary plaque quantification and changes in fractional flow reserve derived from computed tomography across the lesion.

This study sought to evaluate the association between coronary plaque characteristics, changes in the fractional flow reserve (FFR) derived from computed tomography across the lesion (ΔFFRCT), and lesion-specific ischemia using the FFR in patients with suspected or known coronary artery disease. The study assessed coronary computed tomography (CT) angiography stenosis, plaque characteristics, ΔFFRCT, and FFR in 164 vessels of 144 patients. Obstructive stenosis was defined as stenosis ≥50%. An area under the receiver -operating characteristics curve (AUC) analysis was conducted to define the optimal thresholds for ΔFFRCT and the plaque variables. Ischemia was defined as a FFR of ≤0.80. The optimal cut-off value of ΔFFRCT was 0.14. Low-attenuation plaque (LAP) ≥76.23 mm3 and a percentage aggregate plaque volume (%APV) ≥28.91% can be used to predict ischemia independent of other plaque characteristics. The addition of LAP ≥76.23 mm3 and %APV ≥28.91% improved the discrimination (AUC, 0.742 vs. 0.649, P=0.001) and reclassification abilities [category-free net reclassification index (NRI), 0.339, P=0.027; relative integrated discrimination improvement (IDI) index, 0.093, P<0.001] of the assessments compared to the stenosis evaluation alone, and the addition of information about ΔFFRCT ≥0.14 further increased the discrimination (AUC, 0.828 vs. 0.742, P=0.004) and reclassification abilities (NRI, 1.029, P<0.001; relative IDI, 0.140, P<0.001) of the assessments. The addition of the plaque assessment and ΔFFRCT to the stenosis assessments improved the identification of ischemia compared to the stenosis assessment alone.

Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors.

Twenty percent to 40% of patients are affected by angina after percutaneous coronary intervention (PCI), which is associated with anxiety, depression, impaired physical function, and reduced quality of life. Understanding patient and procedural factors associated with post-PCI angina may inform alternative approaches to treatment. Two hundred thirty patients undergoing PCI completed the Seattle Angina Questionnaire (SAQ-7) and European quality of life-5 dimension-5 level (EQ-5D-5L) questionnaires at baseline and 3 months post-PCI. Patients received blinded intracoronary physiology assessments before and after stenting. A post hoc analysis was performed to compare clinical and procedural characteristics among patients with and without post-PCI angina (defined by follow-up SAQ-angina frequency score <100). Eighty-eight of 230 patients (38.3%) reported angina 3 months post-PCI and had a higher incidence of active smoking, atrial fibrillation, and history of previous myocardial infarction or PCI. Compared with patients with no angina at follow-up, they had lower baseline SAQ summary scores (69.48±24.12 versus 50.20±22.59, P<0.001) and EQ-5D-5L health index scores (0.84±0.15 versus 0.69±0.22, P<0.001). Pre-PCI fractional flow reserve (FFR) was lower among patients who had no post-PCI angina (0.56±0.15 versus 0.62±0.13, P=0.003). Percentage change in FFR after PCI had a moderate correlation with angina frequency score at follow-up (r=0.36, P<0.0001). Patients with post-PCI angina had less improvement in FFR (43.1±33.5% versus 67.0±50.7%, P<0.001). There were no between-group differences in post-PCI FFR, coronary flow reserve, or corrected index of microcirculatory resistance. Patients with post-PCI angina had lower SAQ-summary scores (64.01±22 versus 95.16±8.72, P≤0.001) and EQ-5D-5L index scores (0.69±0.26 versus 0.91±0.17, P≤0.001) at follow-up. Larger improvements in FFR following PCI were associated with less angina and better quality of life at follow-up. In patients with stable symptoms, intracoronary physiology assessment can inform expectations of angina relief and quality of life improvement after stenting and thereby help to determine the appropriateness of PCI. URL: https://www. gov; Unique identifier: NCT03259815.

Myocardial Perfusion and Coronary Physiology Assessment of Microvascular Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation-Rationale and Design.

The prevalence of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is 30-68%. Nevertheless, there is still not enough evidence to use invasive assessment of lesion severity, because the hemodynamic milieu of AS may impact the fractional flow reserve (FFR) and non-hyperemic indices. Therefore, the aim of the study is two-fold. First, to measure acute and long-term changes of FFR, index of microvascular resistance (IMR), and coronary flow reserve (CFR) in patients undergoing TAVI procedure. Second, to compare the diagnostic accuracy of intracoronary indices with myocardial perfusion measured by cadmium-zinc-telluride single-photon emission tomography (CZT-SPECT) and find cut-off values defining significant stenosis. We plan to enroll 40 patients eligible for TAVI with intermediate stenosis (30-70%) in the left anterior descending (LAD) coronary artery. In each patient FFR, CFR, and IMR will be measured in addition to myocardial blood flow calculated by CZT-SPECT before and either immediately after TAVI (acute cohort) or in 6 months (late cohort) after the procedure. FFR, CFR, and IMR will be matched with the results of myocardial perfusion measured by CZT-SPECT in the area of LAD. As a result, cut-off values of FFR, CFR, and IMR defining the decreased blood flow will be found.

Differential Improvement in Angina and Health-Related Quality of Life After PCI in Focal and Diffuse Coronary Artery Disease

BackgroundAn increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief. ObjectivesThe aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG). MethodsThis is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score <100. ResultsA total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020). ConclusionsResidual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve [TARGET-FFR]; NCT03259815)

Effect of Atorvastatin on Serial Changesin Coronary Physiology andPlaque Parameters.

The effects of statin on coronary physiology have not been well evaluated. The authors performed this prospective study to investigate changes in coronary flow indexes and plaque parameters, and their associations with atorvastatin therapy in patients with coronary artery disease (CAD). Ninety-five patients with intermediate CAD who received atorvastatin therapy underwent comprehensive physiological assessments with fractional flow reserve (FFR), coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound at the index procedure, and underwent the same evaluations at 12-month follow-up. Optimal low-density lipoprotein cholesterol (LDL-C) was defined as LDL-C<70mg/dL or≥50% reduction from the baseline. The primary endpoint was a change in the FFR. Baseline FFR, minimal lumen area, and percent atheroma volume (PAV) were 0.88 ± 0.05, 3.87 ± 1.28, 55.92 ± 7.30, respectively. During 12months, the percent change in LDL-C was -33.2%, whereas FFR was unchanged (0.87 ± 0.06 at 12months; P=0.694). Vessel area, lumen area, and PAV were significantly decreased (all P values<0.05). The achieved LDL-C level and the change of PAV showed significant inverse correlations with the change in FFR. In patients with optimally modified LDL-C, the FFR had increased (0.87 ± 0.06 vs 0.89 ± 0.07; P=0.014) and the PAV decreased (56.81 ± 6.44% vs 55.18 ± 8.19%; P=0.031), whereas in all other patients, the FFR had decreased (0.88 ± 0.05 vs 0.86 ± 0.06; P=0.025) and the PAV remained unchanged. In patients with CAD, atorvastatin did not change FFR despite a decrease in the PAV. However, in patients who achieved the optimal LDL-C target level with atorvastatin, the FFR had significantly increased with decrease of the PAV. (Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease [FORTE]; NCT01946815).

Improvement in angina pectoris after percutaneous coronary interventions in focal and diffuse coronary artery disease

Abstract Objective To investigate the effect of PCI on patient-reported outcomes in focal and diffuse coronary artery disease (CAD) as defined by the pullback pressure gradient (PPG). Background Improvements in fractional flow reserve (FFR) following PCI are associated with freedom from angina. CAD patterns influence the FFR change after stenting. Therefore, CAD patterns might be essential to assess the likelihood of PCI success in terms of angina relief. Methods This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The 7-item Seattle Angina Questionnaire (SAQ-7) and EuroQol five-level EQ-5D questionnaire (EQ-5D-5L) were administered at baseline and three months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks and the median PPG value was used to define focal and diffuse CAD. Results 103 patients (51 with focal and 52 with diffuse disease) were analyzed. There were no differences in baseline characteristics between patients with focal and diffuse CAD. Patients with focal disease had larger increases in FFR with PCI than those with diffuse disease (0.30±0.14 units vs 0.19±0.12 units, p&amp;lt;0.001). Patients who underwent PCI to focal CAD had significantly higher SAQ-7 summary scores at follow-up compared to those with diffuse CAD (87.1±20.3 vs. 75.6±24.4, mean difference 11.5 [95% CI 2.8 to 20.3], p=0.01). Following PCI, residual angina was present in 39.8% of all patients but was significantly lower among those with treated focal CAD (27.5% vs 51.9%, p-value=0.020). Conclusion Persistent angina after PCI was almost twice as common in patients with diffuse CAD as defined by the pre-PCI PPG. Patients with focal disease reported greater improvement in angina and quality of life with PCI. The likelihood of successful angina relief from PCI can be predicted by the baseline pattern of CAD. Funding Acknowledgement Type of funding sources: None.

Numerical simulation of the blood flow through the coronary artery stenosis: Effects of varying eccentricity

Blockages within arteries, called stenoses, are a common cause of coronary artery disease (CAD). Stenosis is a result of atherosclerotic plaque build-up limits blood flow and hence oxygen and nutrient supplies. Past studies on stenosed arterial flows often assumed stenosis to be axisymmetric in shape. However, medical imaging modalities have shown that stenoses in the coronary arteries are often asymmetric. To address it, an asymmetric stenosis is considered in the model which is based on common dimensions of the left anterior descending artery (LAD). The hemodynamic impacts are studied over a range of degrees of eccentricity (DoE) and degree of stenosis (DoS). Blood flow within the artery is analyzed by solving the incompressible Navier-Stokes equations with both resting and hyperemic flow rates. The wall shear stress (WSS), oscillatory shear index (OSI) and fractional flow reserve (FFR) are calculated.The eccentricity makes the flow deflect away from the model's centerline. Behavior of the deflected flow is significantly altered downstream of the stenosis. Transverse dimension of the recirculation zone grows with increasing DoE, while its longitudinal dimension mainly depends on DoS. Eccentricity also contributes to the development of secondary flow distal to the stenosis. Such complex flow behavior contributes to a further pressure loss and hence a significant change in FFR (<0.8). Calculated WSS and OSI indicate that in actual eccentric stenotic LAD the asymmetric remodeling is anticipated. Thus, consideration of the DoE, along with the DoS, could lead to better patient stratification.

Instantaneous wave-free ratio and fractional flow reserve: effect of variation in left ventricular end diastolic pressure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Among patients with intermediate coronary artery stenosis (50-90%), assessment of functional significance of the lesion by instantaneous wave free ratio (iFR)/ fractional flow reserve (FFR) is recommended in latest guidelines. Though iFR is not much affected by change in hemodynamics compared to FFR, the change in iFR vs FFR due to various hemodynamic factors need a validation. Left ventricular end-diastolic pressure (LVEDP) is one of the hemodynamic factors whose variation and effect on FFR vs iFR is largely unknown. In the present study we evaluated the association of change in LVEDP on the changing pattern of iFR/FFR which may hold a clinical significance especially with percutaneous coronary intervention in heart failure patients. Methods This was a prospective, investigator-initiated, single-center study involving 20 patients with stable coronary artery disease and at least one intermediate coronary lesion (50-90%). The enrolled patients were subjected to both iFR and FFR along with baseline LVEDP measurement. Subsequently, intravenous nitroglycerine infusion was given to reduce LVEDP and corresponding iFR and FFR were re-evaluated. The dynamic changes in iFR and FFR were studied in relation to changes in LVEDP using Pearson’s correlation analysis and linear regression analysis. Results The mean LVEDP was lowered from 16.20 ± 1.54 mmHg to 9.50 ± 1.10 mmHg, the mean iFR and FFR got changed from 0.80 ± 0.12 to 0.76 ± 0.12 mmHg and 0.75 ± 0.09 to 0.72 ± 0.09 mmHg respectively. On Pearson’s correlation analysis, LVEDP change did not show statistically significant correlation (linear relationship) with iFR (p = 0.105, r2 = 0.373) and FFR (p = 0.227, r2 = 0.283) changes across the entire range of stenosis severity and in all vessels. Linear regression analysis did not state any independent correlation between LVEDP and iFR and FFR changes in the study group (p &amp;gt;0.05). The % R2 value for iFR and FFR (as a coefficient of determination) of the regression equation were 13.9% and 8%, which means only these percentages of the total variance in iFR and FFR change were explained by LVEDP changes respectively. There was no serious adverse event related to the procedure. Conclusion To the best of our knowledge, this is the first study comparing the effect of changes in LVEDP on both iFR and FFR simultaneously. In our study, 1 mmHg change in LVEDP was associated with a change in FFR by 0.004 and change in iFR by 0.004 which didn’t reveal any significant association (p = 0.227 and 0.105 respectively). This helps us to put FFR at par with iFR under variable hemodynamics. So either of the variables may be used interchangeably with confidence in varied hemodynamic conditions including patients with heart failure. The correlation was non-significant across entire range of stenosis severity, irrespective of sex, age, diabetes and hypertension. This study sets platform for further research with larger number of heterogeneous patient population. Abstract Figure. Box whisker plot

The coronary and microcirculatory measurements in patients with aortic valve stenosis study: rationale and design.

Although concomitant coronary artery disease (CAD) is frequent in patients with severe aortic stenosis (AS), hemodynamic assessment of CAD severity in patients undergoing valve replacement for severe AS is challenging. Myocardial hypertrophic remodeling interferes with coronary blood flow and may influence the values of fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). The aim of the current study is to investigate the effect of the AS and its treatment on current indices used for evaluation of CAD. We will compare intracoronary hemodynamics before, immediately after, and 6 mo after aortic valve replacement (AVR) when it is expected that microvascular function has improved. Furthermore, we will compare FFR and resting full-cycle ratio (RFR) with myocardial perfusion single-photon emission-computed tomography (SPECT) as indicators of myocardial ischemia in patients with AS and CAD. One-hundred consecutive patients with AS and intermediate CAD will be prospectively included. Patients will undergo pre-AVR SPECT and intracoronary hemodynamic assessment at baseline, immediately after valve replacement [if transcatheter AVR (TAVR) is chosen], and 6 mo after AVR. The primary end point is the change in FFR 6 mo after AVR. Secondary end points include the acute change of FFR after TAVR, the diagnostic accuracy of FFR versus RFR compared with SPECT for the assessment of ischemia, changes in microvascular function as assessed by the index of microcirculatory resistance (IMR), and the effect of these changes on FFR. The present study will evaluate intracoronary hemodynamic parameters before, immediately after, and 6 mo after AVR in patients with AS and intermediate coronary stenosis. The understanding of the impact of AVR on the assessment of FFR, NHPR, and microvascular function may help guide the need for revascularization in patients with AS and CAD planned for AVR.

Trans-stenotic pressure gradient as derived from CT improves patient management: ADVANCE registry

Abstract Background The change in fractional flow reserve derived from CT (FFRCT) value across a coronary stenosis (ΔFFRCT) improves the physiological characterization of coronary artery disease (CAD). The role of ΔFFRCT in guiding risk-stratification and downstream testing in patients with stable CAD is unknown. Purpose To investigate the incremental value of ΔFFRCT at predicting early revascularization and improving efficacy of resource utilization. Methods Patients with CAD on CT coronary angiography (CTCA) were enrolled in an international multicenter registry. Patients with non-evaluable FFRCT analysis were excluded. The CTCA was assessed for: stenosis severity as per CAD-Reporting and Data System (CAD-RADS), lesion length and lesion-specific FFRCT measured 2 cm distal to stenosis. Risk factors and actual treatment (revascularization vs medical therapy) at 90-day follow-up were recorded. Multivariable logistic regression analysis for early revascularization was conducted. The incremental discrimination for revascularization prediction was compared among 3 models (model 1: risk factors + lesion length and location + CAD-RADS; model 2: model 1 + lesion-specific FFRCT; model 3: model 2 + ΔFFRCT). Simulating ICA referral for patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, the potential impact of ΔFFRCT at reducing ICA referral and improving the ratio of subsequent revascularization was assessed. Results Of 4730 patients (66±10 years; 34% female), 2092 (42.7%) underwent ICA and 1168 (24.7%) underwent early revascularization. With increasing ΔFFRCT, a higher incidence of revascularization (Figure 1A) and an increase in the revascularization to ICA ratio was observed (Figure 1B). ΔFFRCT &amp;gt;0.13 was the optimal cut-off for predicting revascularization as determined by the Youden index. ΔFFRCT remained an independent predictor for early revascularization (odds ratio per 0.05 increase with 95% CI, 1.31 [1.26–1.35]; p&amp;lt;0.0001) after adjusting for risk factors, CAD-RADS, lesion length and location, and FFRCT. Among the 3 models, model 3, which included ΔFFRCT showed the highest AUC and improved discrimination power compared to model 2 (0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p&amp;lt;0.0001] (Figure 2), with the greatest incremental value for ΔFFRCT observed in patients with lesion-specific FFRCT between 0.71–0.80. In patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, a diagnostic strategy incorporating ΔFFRCT &amp;gt;0.13 would potentially reduce ICA referral by 32.2% (1638 to 1110) and improve the revascularization to ICA ratio from 65.2% [1068/1638] to 73.1% [811/1110]. Conclusions The characterization of CAD with ΔFFRCT improves the identification of patients requiring early revascularization as compared to a standard diagnostic strategy of CTCA with FFRCT, particularly for those with lesion-specific FFRCT of 0.71–0.80. ΔFFRCT has the potential to aid decision making for ICA referral and improve the efficiency of resource utilization. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): HeartFlow, Inc., Redwood City, CA, USA ΔFFRCT and actual treatmentROC curve for early revascularization

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe role of change in fractional flow reserve derived from CT (FFRCT) across coronary stenoses (ΔFFRCT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown. ObjectivesTo investigate the incremental value of ΔFFRCT in predicting early revascularization and improving efficiency of catheter laboratory utilization. MaterialsPatients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFRCT was measured 2 ​cm distal to stenosis. ΔFFRCT was manually measured as the difference of FFRCT across visible stenosis. ResultsOf 4730 patients (66 ​± ​10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFRCT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ​< ​0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFRCT. Among the 3 models (model 1: risk factors ​+ ​stenosis type and location ​+ ​CAD-RADS; model 2: model 1 ​+ ​FFRCT; model 3: model 2 ​+ ​ΔFFRCT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ​< ​0.001), with the greatest incremental value for FFRCT 0.71–0.80. ΔFFRCT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, a diagnostic strategy incorporating ΔFFRCT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ​< ​0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%. ConclusionsΔFFRCT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFRCT, particularly for those with FFRCT 0.71–0.80. ΔFFRCT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.

Variation of computed tomographic angiography-based fractional flow reserve after transcatheter aortic valve implantation.

We sought to identify the impact of transcatheter aortic valve implantation (TAVI) on changes of fractional flow reserve computed tomography (FFRCT) values and the associated clinical impact. A retrospective analysis was done with CT obtained pre-TAVI, prior to hospital discharge and at 1-year follow-up, which provided imaging sources for the calculation of FFRCT values based on an online platform. A total of 190 patients were enrolled. Patients with pre-procedural FFRCT value > 0.80 (i.e., negative) and ≤ 0.80 (i.e., positive) demonstrated a significantly opposite change in the value after TAVI (0.8798 vs. 0.8718, p < 0.001 and 0.7634 vs. 0.8222, p < 0.001, respectively). The history of coronary artery disease (CAD) was identified as an independent predictor for FFRCT changing from negative to positive after TAVI (odds ratio [OR] 2.927, 95% confidence interval [CI] 1.130-7.587, p = 0.027), with lesions more severely stenosed (OR 1.039, 95% CI 1.003-1.076, p = 0.034) and in left anterior descending coronary artery (LAD) (OR 3.939, 95% CI 1.060-14.637, p = 0.041) being prone to change. TAVI directly brings improvement in FFRCT values in patients with compromised coronary flow. Patients with a history of CAD, especially with lesions more severely stenosed and in LAD, were under risk of FFRCT changing from negative to positive after TAVI. •The effect of TAVI on coronary hemodynamics might be influenced by different ischemic severity and coronary territories reflected by FFRCT values. •As different FFRCT variations did not impact outcomes of TAVI patients, AS, but not coronary issues, may be the primary problem to affect, which needs further validation.

Coronary artery height differences and their effect on fractional flow reserve.

Fractional flow reserve (FFR) uses pressure-based measurements to assess the severity of a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximal aortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, may impact FFR calculation. One hundred computed tomography coronary angiographies were used to measure height differences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. This was tested in a simulation of intermediate coronary stenosis to give the "corrected FFR" (cFFR) and percentage of values, which crossed a threshold of 0.8. The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm, distal circumflex (Cx) -3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV) -5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, -0.027 in the Cx, -0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatment threshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases. There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values.

Evaluation of effects of cardiac resynchronization on coronary blood flow by coronary flow reserve and in patients with İdiopathic dilated cardiomyopathy: Does it predict the response?

Background: The results of previous studies evaluating the effects of cardiac resynchronization therapy (CRT) on myocardial blood flow (MBF) and their relation with the response to CRT are conflicting. Materials and Methods: Sixty-one patients diagnosed with idiopathic dilated cardiomyopathy (IDC), a functional capacity (New York Heart Association [NYHA]) Class II or III, and left bundle branch block (LBBB) (QRS width >150 ms) were enrolled in the study. We aimed to evaluate the effects of CRT on MBF in patients with IDC and LBBB by coronary flow reserve (CFR) measurements and thereby tried to predict the responders. Results: Sixty-one patients with IDC were enrolled. CFR and hyperemic fractional flow reserve (FFR) increased after CRT. The only parameter affecting the increase in CFR was the change in FFR after CRT. Then, 44 patients who responded to the CRT treatment at 6 months were compared with 17 patients who did not. Left ventricle outflow tract time-velocity integral (LVOT-TVI), stroke volume (SV) and cardiac output index (COi) was detected significantly higher also left ventricular end-diastolic pressure (LVEDP) was lower in the CRT responders. However, there were no significant differences in coronary flow velocity measurements between the two groups. Moreover the regression analysis revealed that the baseline NYHA class, LVOT TVI, SV, COi, and LVEDP, which were changed due to increased blood flow after CRT implantation, is not associated with response to CRT. Conclusions: Our results suggest that MBF increased after CRT in patients with IDC probably by improving microvascular functions. However, the response to CRT treatment is not related to the changes in the coronary blood flow velocities after CRT.

Influence of caffeine intake on intravenous adenosine-induced fractional flow reserve

Abstract Background This study evaluated whether caffeine abstention is required before fractional flow reserve (FFR) measurement by intravenous adenosine triphosphate (ATP) administration in Japanese patients. Methods and results This study was a subanalysis of a previously published study and a total of 208 intermediate lesions that underwent FFR measurements were enrolled for this analysis. Hyperemia was induced by continuous intravenous ATP infusion at 150μg/kg/min (IVATP150) and 210μg/kg/min (IVATP210), and by intracoronary administration of nicorandil 2mg (ICNIC2mg) as a reference standard. The degree of change in the FFR value both after IVATP150 and after IVATP210, as compared with the FFR value after ICNIC2mg was similar between the caffeine and non-caffeine groups (−0.04±0.05 vs. −0.04±0.07, and 0.00±0.02 vs. 0.01±0.02, respectively). In patients who consumed caffeine before the FFR measurement, the degree of FFR change was independent of the time interval (&amp;lt;12 hours, 12–24 hours, and 24–48 hours) between caffeine intake and catheterization both after IVATP150 and ICNIC2mg and after IVATP210 and ICNIC2mg. Conclusion When compared with the FFR value after ICNIC2mg, the degree of change in the FFR value both after IVATP150 and after IVATP210 remained similar regardless of caffeine intake. Strict caffeine abstention before intravenous ATP-induced FFR measurement may not be required in clinical practice. Funding Acknowledgement Type of funding source: None