Hyperemic Stenosis Resistance Research Articles

Impact of hyperaemic stenosis resistance on long-term outcomes of stable angina in the ILIAS Registry.

The hyperaemic stenosis resistance (HSR) index was introduced to provide a more comprehensive indicator of the haemodynamic severity of a coronary lesion. HSR combines both the pressure drop across a lesion and the flow through it. As such, HSR overcomes the limitations of the more traditional fractional flow reserve (FFR) or coronary flow reserve (CFR) indices. We aimed to identify the diagnostic and prognostic value of HSR and evaluate the clinical implications. Patients with chronic coronary syndromes (CCS) and obstructive coronary artery disease were selected from the multicentre ILIAS Registry. For this study, only patients with combined Doppler flow and pressure measurements were included. A total of 853 patients with 1,107 vessels were included. HSR more accurately identified the presence of inducible ischaemia compared to FFR and CFR (area under the curve 0.71 vs 0.66 and 0.62, respectively; p<0.005 for both). An abnormal HSR measurement was an independent and important predictor of target vessel failure at 5-year follow-up (hazard ratio 3.80, 95% confidence interval: 2.12-6.73; p<0.005). In vessels deferred from revascularisation, HSR seems to identify more accurately those vessels that may benefit from revascularisation rather than FFR and/or CFR. The present study affirms the theoretical advantages of the HSR index for the detection of ischaemia-Âinducing coronary lesions in a large CCS population. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry], ClinicalTrials.gov: NCT04485234).

Impact of stenosis resistance and coronary flow capacity on fractional flow reserve and instantaneous wave-free ratio discordance: acombined analysis of DEFINE-FLOW and IDEAL.

The pressure-derived parameters fractional flow reserve (FFR) and the emerging instantaneous wave-free ratio (iFR) are the most widely applied invasive coronary physiology indices to guide revascularisation. However, approximately 15-20% of intermediate stenoses show discordant FFR and iFR, and therapeutical consensus is lacking. We sought to associate hyperaemic stenosis resistance index, coronary flow reserve (CFR) and coronary flow capacity (CFC) to FFR/iFR discordance. We assessed pressure and flow measurements of 647 intermediate lesions (593patients) of two multi-centre international studies. FFR and iFR were discordant in 15% of all lesions (97 out of 647). FFR+/iFR- lesions had similar hyperaemic average peak velocity (hAPV), CFR and CFC as FFR-/iFR- lesions, whereas FFR-/iFR+ lesions had similar hAPV, CFR and CFC as FFR+/iFR+ lesions (p > 0.05 for all). FFR+/iFR- lesions were associated with lower baseline stenosis resistance, but not hyperaemic stenosis resistance, compared with FFR-/iFR+ lesions (p < 0.001). Discordance with FFR+/iFR- is characterised by maximal flow values, CFR, and CFC patterns similar to FFR-/iFR- concordance that justifies conservative therapy. Discordance with FFR-/iFR+ on the other hand, is characterised by low flow values, CFR, and CFC patterns similar to iFR+/FFR+ concordance that may benefit from percutaneous coronary intervention.

Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy

ObjectiveThis study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary...

Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment.

Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest, LCAhyp, RCArest and RCAhyp, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom=1.55±0.35, RCAco-dom=1.40±0.27, RCAnon-dom=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R2 =0.018, p=0.03 and DSVR x coronary flow reserve R2 <0.001, p=0.98). In patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.

Characterization of quantitative flow ratio and fractional flow reserve discordance using doppler flow and clinical follow-up.

The physiological mechanisms of quantitative flow ratio and fractional flow reserve disagreement are not fully understood. We aimed to characterize the coronary flow and resistance profile of intermediate stenosed epicardial coronary arteries with concordant and discordant FFR and QFR. Post-hoc analysis of the DEFINE-FLOW study. Anatomical and Doppler-derived physiological parameters were compared for lesions with FFR+QFR- (n = 18) vs. FFR+QFR+ (n = 43) and for FFR-QFR+ (n = 34) vs. FFR-QFR- (n = 139). The association of QFR results with the two-year rate of target vessel failure was assessed in the proportion of vessels (n = 195) that did not undergo revascularization. Coronary flow reserve was higher [2.3 (IQR: 2.1-2.7) vs. 1.9 (IQR: 1.5-2.4)], hyperemic microvascular resistance lower [1.72 (IQR: 1.48-2.31) vs. 2.26 (IQR: 1.79-2.87)] and anatomical lesion severity less severe [% diameter stenosis 45.5 (IQR: 41.5-52.5) vs. 58.5 (IQR: 53.1-64.0)] for FFR+QFR- lesions compared with FFR+QFR+ lesions. In comparison of FFR-QFR+ vs. FFR-QFR- lesions, lesion severity was more severe [% diameter stenosis 55.2 (IQR: 51.7-61.3) vs. 43.4 (IQR: 35.0-50.6)] while coronary flow reserve [2.2 (IQR: 1.9-2.9) vs. 2.2 (IQR: 1.9-2.6)] and hyperemic microvascular resistance [2.34 (IQR: 1.85-2.81) vs. 2.57 (IQR: 2.01-3.22)] did not differ. The agreement and diagnostic performance of FFR using hyperemic stenosis resistance (> 0.80) as reference standard was higher compared with QFR and coronary flow reserve. Disagreement between FFR and QFR is partly explained by physiological and anatomical factors. Clinical Trials Registration https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

Computational Assessment of Hemodynamic Significance in Patients With Intramural Anomalous Aortic Origin of the Coronary Artery Using Virtually Derived Fractional Flow Reserve and Downstream Microvascular Resistance.

Anomalous aortic origin of a coronary artery (AAOCA) is the second most common cause of sudden cardiac death in young athletes. One of the hypothesized mechanisms of ischemia in these patients is the lateral compression of the anomalous artery with an intramural or interarterial course. The presence of a narrowing in the anomalous artery will cause physiologic changes in downstream resistance that should be included for computational assessment of possible clinical ramifications. In this study, we created different compression levels, i.e., proximal narrowing, in the intramural course of a representative patient model and calculated hyperemic stenosis resistance (HSR) as well as virtual fractional flow reserve (vFFR). Models also included the effect of the distal hyperemic microvascular resistance (HMR) on vFFR. Our results agreed with similar FFR studies indicating that FFR is increased with increasing HMR and that different compression levels could have similar FFR depending on the HMR. For example, vFFR at HSR: 1.0-1.3 and HMR: 2.30 mmHg/cm/s is 0.68 and close to vFFR at HSR: 0.6-0.7 and HMR: 1.6 mmHg/cm/s, which is 0.7. The current findings suggest that functional assessment of anomalous coronary arteries through FFR should consider the vascular resistance distal to the narrowing in addition to the impact of a proximal narrowing and provides computational approaches for implementation of these important considerations.

Association of Quantitative Flow Ratio with Lesion Severity and Its Ability to Discriminate Myocardial Ischemia.

Background and ObjectivesQuantitative flow ratio (QFR) is an angiography-based technique for functional assessment of coronary artery stenosis. This study investigated the response of QFR to different degree of stenosis severity and its ability to predict the positron emission tomography (PET)-defined myocardial ischemia.MethodsFrom 109 patients with 185 vessels who underwent both 13N-ammonia PET and invasive physiological measurement, we compared QFR, fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) for the responses to the different degree of anatomical (percent diameter stenosis [%DS]) and hemodynamic (relative flow reserve [RFR], coronary flow reserve, hyperemic stenosis resistance, and stress myocardial flow) stenosis severity and diagnostic performance against PET-derived parameters.ResultsQFR, FFR, and iFR showed similar responses to both anatomic and hemodynamic stenosis severity. Regarding RFR, the diagnostic accuracy of QFR was lower than FFR (76.2% vs. 83.2%, p=0.021) and iFR (76.2% vs. 84.3%, p=0.031). For coronary flow capacity (CFC), QFR showed a lower accuracy than iFR (74.1% vs. 82%, p=0.031) and lower discriminant function than FFR (area under curve: 0.74 vs. 0.79, p=0.044). Discordance between QFR and FFR or iFR was shown in 14.6% of cases and was driven by the difference in %DS and heterogeneous distribution of PET-derived RFR and stress myocardial blood flow.ConclusionsQFR demonstrated a similar response to different anatomic and hemodynamic stenosis severity as FFR or iFR. However, its diagnostic performance was inferior to FFR and iFR when PET-derived RFR and CFC were used as a reference.

FFR=1.0 flow changes after percutaneous coronary intervention

BackgroundThe present study investigated the relationships between physiological indices and increased coronary flow during percutaneous coronary intervention (PCI) using a novel index of “anticipated maximum flow” [AMF; theoretical coronary flow of fractional flow reserve (FFR) = 1]. FFR-guided PCI aims to increase coronary flow, whereas recent studies have reported that PCI does not necessarily increase coronary flow despite improvement in FFR. MethodsThis retrospective analysis was performed in 71 functionally significant lesions treated with elective PCI. AMF obtained by hyperemic average peak coronary flow velocity (h-APV) divided by FFR would not change after PCI given the constant microvascular resistance, which is the assumption of FFR as a surrogate of coronary flow. We evaluated the relationship between AMF and coronary flow during PCI. ResultsPost-PCI AMF was significantly different from pre-PCI AMF (p = 0.022), which impacted discordance between FFR improvement and change in coronary flow. Coronary flow increase >50% was associated with smaller minimum lumen diameter (p = 0.010), greater diameter stenosis (p = 0.003), lower pre-PCI FFR (p < 0.001), lower pre-PCI coronary flow reserve (p = 0.001), higher pre-PCI hyperemic stenosis resistance (p < 0.001), lower pre-PCI h-APV (p = 0.001), and lower pre-PCI AMF (p = 0.031). Pre-PCI AMF provided significant incremental predictive capability for coronary flow increase >50% when added to the clinical model including pre-PCI FFR. ConclusionPre-PCI AMF provided incremental ability to predict increased coronary flow after PCI and impacted the discordance between FFR improvement and increased coronary flow.

Comparison of fractional flow reserve, instantaneous wave-free ratio and a novel technique for assessing coronary arteries with serial lesions.

Physiological indices such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR) and resting distal coronary to aortic pressure (Pd/Pa) are increasingly used to guide revascularisation. However, reliable assessment of individual stenoses in serial coronary disease remains an unmet need. This study aimed to compare conventional pressure-based indices, a reference Doppler-based resistance index (hyperaemic stenosis resistance [hSR]) and a recently described mathematical correction model to predict the contribution of individual stenoses in serial disease. Resting and hyperaemic pressure wire pullbacks were performed in 54 patients with serial disease. For each stenosis, FFR, iFR, and Pd/Pa were measured by the translesional gradient in each index and the predicted FFR (FFRpred) derived mathematically from hyperaemic pullback data. "True" stenosis significance by each index was assessed following PCI of the accompanying stenosis or measurements made in a large disease-free branch. In 27 patients, Doppler average peak flow velocity (APV) was also measured to calculate hSR (hSR=∆P/APV, where ∆P=translesional pressure gradient). FFR underestimated individual stenosis severity, inversely proportional to cumulative FFR (r=0.5, p<0.001). Mean errors for FFR, iFR and Pd/Pa were 33%, 20% and 24%, respectively, and 14% for FFRpred (p<0.001). Stenosis misclassification rates based on FFR 0.80, iFR 0.89 and Pd/Pa 0.91 thresholds were not significantly different (17%, 24% and 20%, respectively) but were higher than FFRpred (11%, p<0.001). Apparent and true hSR correlated strongly (r=0.87, p<0.001, mean error 0.19±0.3), with only 7% of stenoses misclassified. Individual stenosis severity is significantly underestimated in the presence of serial disease, using both hyperaemic and resting pressure-based indices. hSR is less prone to error but challenges in optimising Doppler signals limit clinical utility. A mathematical correction model, using data from hyperaemic pressure wire pullback, produces similar accuracy to hSR and is superior to conventional pressure-based indices.

Contribution of Age-Related Microvascular Dysfunction to Abnormal Coronary: Hemodynamics in Patients With Ischemic Heart Disease

ObjectivesThis study sought to investigate the contribution of age-related microcirculatory dysfunction to abnormal coronary hemodynamics in patients with coronary atherosclerosis. BackgroundImpairment in myocardial blood supply in patients with coronary atherosclerosis can be accentuated due to age-related changes in microcirculatory function. MethodsIntracoronary pressure and flow were measured with the Doppler technique in 299 vessels (228 patients), and the thermodilution technique in 120 vessels (99 patients). In 172 patients, Doppler measurements were also performed in unobstructed vessels. Associations of coronary hemodynamics with aging were studied in both the stenosed and unobstructed arteries. ResultsAging was associated with a progressive increase in minimal microvascular resistance and a progressive decrease in hyperemic flow in both obstructed and nonobstructed coronary arteries. As such, coronary flow reserve decreased with advancing age. Epicardial stenosis severity assessed by resting Pd/Pa, basal stenosis resistance index, and hyperemic stenosis resistance index was equivalent across age groups. By contrast, fractional flow reserve increased with advancing age. Consequently, the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of concomitant focal epicardial and diffuse or microvascular disease (relative risk: 1.6; 95% confidence interval: 1.1 to 2.3; p = 0.017) increased with advancing age, whilst the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of non–flow-limiting stenosis with a healthy microcirculation decreased (relative risk: 0.7; 95% CI: 0.5 to 1.0; p = 0.022). ConclusionsAging is associated with progressive pan-myocardial impairment of coronary vasodilatory capacity due to an increase in minimal microvascular resistance. Concomitant aging-related impairment in microvascular function impacts the pathophysiology of ischemic heart disease in the individual patient and is not adequately identified by hyperemic coronary pressure measurements alone.

Pressure- and Velocity-Based Physiological Assessment of Stenotic Lesions at Hyperemia in Superficial Femoral Artery Disease: Importance of Hyperemic Stenosis Resistance.

Background: In superficial femoral artery (SFA) stenosis, stenosis resistance may increase, but the relationship between stenosis resistance and stenotic severity remains to be seen. This study aimed to investigate the physiological response, through a hyperemic condition, and the pathophysiological significance of Doppler flow and stenosis resistance in SFA.Methods: Twenty-four limbs with focal stenosis of the SFA were analyzed. We assessed the fractional flow reserve (FFR), hyperemic stenosis resistance (h-SR), and vascular flow reserve (VFR) of the SFA with a pressure/Doppler flow sensor-tipped combination guidewire before and after endovascular therapy (EVT).Results: FFR, h-SR, and VFR changed significantly after EVT. h-SR was more strongly correlated with % area stenosis, measured by intravascular ultrasound than FFR (FFR: r=−0.716, h-SR: r=0.741, p<0.0001, respectively). However, VFR was not associated with % area stenosis. A receiver operating characteristic curve showed cut-offs h-SR >0.36 mmHg·sec/cm, and FFR <0.88 predicted >75% area stenosis with area under curves of 0.883 and 0.828, respectively.Conclusion: h-SR can indicate stenotic severity in an SFA focal lesion more prominently than FFR and may be a new physiological index to determine indication for EVT. VFR was not feasible for assessment in SFA focal stenosis.

TCT-464 Diagnostic Classification of the coronary flow velocity reserve and hyperemic stenosis resistance index using Contrast media

TCT-464 Diagnostic Classification of the coronary flow velocity reserve and hyperemic stenosis resistance index using Contrast media

Coronary circulation: Pressure/flow parameters for assessment of ischemic heart disease

Both invasive and non-invasive parameters have been reported for assessment of the physiological status of the coronary circulation. Fractional flow reserve and coronary (or myocardial) flow reserve may be obtained by invasive or non-invasive means. These metrics of coronary stenosis severity have achieved wide clinical acceptance for guiding revascularization decisions and risk stratification. Other indices are obtained invasively (e.g., instantaneous wave-free ratio, iFR; hyperemic stenosis resistance) or non-invasively (e.g., PET absolute myocardial blood flow (mL/min/g)) and have been used for the same purposes. Both iFR, and whole-cycle distal coronary to aortic mean pressure (Pd/Pa) are measured under basal condition and used for assessment of hemodynamic stenosis severity as is index of basal stenosis resistance (BSR). These metrics typically are dichotomized at an empirically derived cut point into “normal” and “abnormal” categories for purposes of clinical decision making and data analysis. Once dichotomized the indices do not always point in the same direction and so confusion may arise. This review, therefore, will present basic principles relevant to understanding commonly employed metrics of the physiological status of the coronary circulation, potential strengths and weaknesses, and hopefully an improved appreciation of the clinical information provided by each.

Similarity and Difference of Resting Distal to Aortic Coronary Pressure and Instantaneous Wave-Free Ratio

BackgroundInstantaneous wave-free ratio (iFR) has been used in clinical practice to identify functionally significant stenosis and to guide treatment strategy. However, there are limited clinical data regarding another resting pressure-derived index, resting distal to aortic coronary pressure (Pd/Pa), and similarities and differences between resting Pd/Pa and iFR. ObjectivesThe authors investigated the changes in resting Pd/Pa and iFR according to anatomic and hemodynamic stenosis severity and their prognostic implications. MethodsFrom the 3V FFR-FRIENDS (Clinical Implication of 3-vessel Fractional Flow Reserve) and the IRIS-FFR (Study of the Natural History of FFR Guided Percutaneous Coronary Intervention) studies, 1,024 vessels (n = 435) with available pre-intervention resting Pd/Pa and iFR were used to explore the changes in resting physiological indices according to percent diameter stenosis. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indices according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between physiological indices and the risk of 2-year major adverse cardiac events (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) were analyzed among 375 deferred patients. ResultsThere was a significant linear correlation between resting Pd/Pa and iFR (R = 0.970; p < 0.001, iFR = 1.370 × resting Pd/Pa − 0.370). Both resting Pd/Pa and iFR changed significantly according to percent diameter stenosis, basal and hyperemic stenosis resistance, and hyperemic absolute myocardial blood flow (all p values <0.001). Percent difference of iFR according to the increase in anatomic and hemodynamic severity was higher than that of resting Pd/Pa. Both resting Pd/Pa and iFR showed a significant association with the risk of 2-year MACE (resting Pd/Pa hazard ratio [per 0.10 increase]: 0.480; 95% confidence interval: 0.250 to 0.923; p = 0.027; iFR hazard ratio [per 0.1 increase]: 0.586; 95% confidence interval: 0.373 to 0.919; p = 0.020) in deferred patients. However, the difference between the upper- and lower-bound estimated MACE rates according to the approximate measurement variability of each index was significantly higher with resting Pd/Pa compared with iFR (resting Pd/Pa 3.85 ± 4.00% and iFR 3.27 ± 3.39%; p < 0.001). ConclusionsBoth resting Pd/Pa and iFR showed similar associations with anatomic and hemodynamic stenosis severity and the risk of MACE. However, iFR was more sensitive to the difference in stenosis severity and showed a lower maximum difference in estimated MACE risk influenced by the measurement variability compared with resting Pd/Pa. (Clinical Implication of 3-Vessel Fractional Flow Reserve [3V FFR-FRIENDS]; NCT01621438; and Study of the Natural History of FFR Guided Percutaneous Coronary Intervention [IRIS-FFR]; NCT01366404)

Evaluation of lesion flow coefficient for the detection of coronary artery disease in patient groups from two academic medical centers.

In this study, lesion flow coefficient (LFC: ratio of % area stenosis [%AS] to the square root of the ratio of the pressure drop across the stenosis to the dynamic pressure in the throat region), that combines both the anatomical (%AS) and functional measurements (pressure and flow), was assessed for application in a clinical setting. Pressure, flow, and anatomical values were obtained from patients in 251 vessels from two different centers. Fractional flow reserve (FFR), Coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR) and hyperemic microvascular index (HMR) were calculated. Anatomical data was corrected for the presence of guidewire and the LFC values were calculated. LFC was correlated with FFR, CFR, HSR, HMR, individually and in combination with %AS. The p<0.05 was used for statistical significance. LFC correlated significantly when the FFR (pressure-based), CFR (flow-based), and anatomical measure %AS were combined (r=0.64; p<0.05). Similarly, LFC correlated significantly when HSR, HMR, and %AS were combined (r=0.72; p<0.05). LFC was able to significantly (p<0.05) distinguish between the two concordant and the two discordant groups of FFR and CFR, corresponding to the clinically used cut-off values (FFR=0.80 and CFR=2.0). The LFC could also significantly (p<0.05) distinguish between the normal and abnormal microvasculature conditions in the presence of non-significant epicardial stenosis, while the comparison was borderline significant (p=0.09) in the presence of significant stenosis. LFC, a parameter that combines both the anatomical and functional end-points, has the potential for application in a clinical setting for CAD evaluation.

Discordance Between Fractional Flow Reserve and Coronary Flow Reserve: Insights From Intracoronary Imaging and Physiological Assessment

ObjectivesThe aim of this study was to investigate the epicardial and microvascular substrates associated with discordances between fractional flow reserve (FFR) and coronary flow reserve (CFR) values. BackgroundDiscordances between FFR and CFR remain poorly characterized. MethodsFFR, hyperemic stenosis resistance (HSR), and intravascular ultrasound were performed as indexes of epicardial function and CFR and hyperemic microvascular resistance (HMR) as measures of microvascular function in 94 patients with moderate coronary stenosis. Maximal plaque burden (PBmax), HSR, and HMR were calculated in 4 quadrants based on values of FFR ≤0.80 and CFR ≤2.0 as follows: concordant normal (preserved FFR and CFR), concordant abnormal (low FFR and CFR), discordant low FFR and preserved CFR, and discordant preserved FFR and low CFR. ResultsSixty-four patients (68%) had concordant FFR and CFR findings, and 30 patients (32%) had discordant FFR and CFR. Compared with patients with preserved FFR and CFR, those with low FFR and CFR had higher PBmax (p = 0.003), higher HSR (p < 0.001), and similar HMR. Among patients with preserved FFR, those with reduced CFR had similar PBmax and HSR but a trend toward higher HMR (p = 0.058) compared with patients with preserved CFR. Among patients with reduced FFR, those with preserved CFR had lower PBmax (p = 0.004), a trend toward lower HSR (p = 0.065), and lower HMR (p = 0.03) compared with patients with reduced CFR. Furthermore, compared with patients with preserved FFR and low CFR, those with low FFR and preserved CFR had higher HSR (p = 0.022) but lower HMR (p = 0.003). ConclusionsIn patients with moderate coronary stenosis, preserved FFR and low CFR is associated with increased microvascular resistance, while low FFR and preserved CFR has modest epicardial stenosis and preserved microvascular function.

The IMPACT Study (Influence of Sensor-Equipped Microcatheters on Coronary Hemodynamics and the Accuracy of Physiological Indices of Functional Stenosis Severity).

The Navvus pressure sensor-equipped microcatheter allows to measure functional stenosis severity over a work-horse guidewire and is used as a more feasible alternative to regular sensor-equipped wires. However, Navvus is larger in diameter than contemporary sensor-equipped guidewires and may, thereby, influence functional measurements. The present study evaluates the hemodynamic influence of the Navvus microcatheter. In patients with intermediate coronary stenosis, coronary pressure and flow velocity were measured using a dual sensor-equipped guidewire before and after introduction of Navvus. Patients were randomized to microcatheter-first or guidewire-first measurement. The primary end point was the difference in hyperemic stenosis resistance index between measurements before and after introduction of Navvus. Measurements were completed in 28 patients (28 stenoses). Mean hyperemic stenosis resistance was 0.37±0.19 Hg/cm/s for wire-only assessment and 0.48±0.26 Hg/cm/s after Navvus introduction (P<0.001). Bland-Altman analysis documented a mean bias of +0.11 Hg/cm/s (limits of agreement: -0.13 to 0.36), proportional to mean hyperemic stenosis resistance (Spearman ρ =0.61; P=0.001). Passing-Bablok analysis revealed absence of a constant difference but significant proportional difference between the methods. Mean fractional flow reserve was 0.86±0.06 for wire-only assessment and 0.82±0.07 after Navvus introduction (P<0.001). Bland-Altman analysis documented a mean bias of -0.033 (limits of agreement: -0.09 to 0.03), proportional to mean fractional flow reserve (Spearman ρ =0.40; P=0.036). Passing-Bablok analysis revealed significant constant and proportional differences between methods. Similar results were documented for resting indices of stenosis severity. Introduction of the Navvus microcatheter leads to clinically relevant stenosis severity overestimation in intermediate stenosis.

Basal stenosis resistance index derived from simultaneous pressure and flow velocity measurements.

Vasodilator-free basal stenosis resistance (BSR) equals fractional flow reserve (FFR) accuracy for ischaemia-inducing stenoses. Nonetheless, basal haemodynamic variability may impair BSR accuracy compared with hyperaemic stenosis resistance (HSR). We evaluated the influence of basal haemodynamic variability, as encountered in practice, on BSR accuracy versus HSR when derived from simultaneous pressure and flow velocity measurements, and determined its diagnostic performance for HSR-defined significant stenoses. Simultaneous coronary pressure and flow velocity were obtained in 131 stenoses. The impact of basal haemodynamic conditions on BSR was evaluated by means of their relationship with the relative difference between BSR and HSR. Diagnostic performance of BSR, FFR, iFR, and resting Pd/Pa was assessed by comparing the area under the curve (AUC), using HSR as reference standard. The relative difference between BSR and HSR was not associated with basal heart rate, aortic pressure or rate pressure product. Among all stenoses, as well as within the 0.6-0.9 FFR range, BSR AUC was significantly greater than resting Pd/Pa and iFR AUC; all other AUCs were equivalent. With simultaneous pressure and flow velocity measurements, basal conditions do not systematically limit BSR accuracy compared with HSR. Consequently, diagnostic performance of BSR is equivalent to FFR, and closely approximates HSR.

Diagnostic cutoff for pressure drop coefficient in relation to fractional flow reserve and coronary flow reserve: A patient-level analysis.

Functional assessment of intermediate coronary stenosis during cardiac catheterization is conducted using diagnostic parameters like fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR), and hyperemic microvascular resistance (HMR). CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a nondimensional index derived from fundamental fluid dynamic principles, based on a combination of intracoronary pressure, and flow measurements may improve the functional assessment of coronary lesion severity. Patient-level data pertaining to 350 intracoronary pressure and flow measurements across coronary stenoses was assessed to evaluate CFR, FFR, HSR, HMR, and CDP. CDP was calculated as (ΔP)/(0.5 × ρ × APV(2)). The density of blood (ρ) was assumed to be 1.05 g/cm(3). The correlation of current diagnostic parameters (CFR, FFR, HSR, and HMR) with CDP was evaluated. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off point of CDP, corresponding to the clinically used cut-off values (FFR = 0.80 and CFR = 2.0). CDP correlated significantly with FFR (r = 0.81, P < 0.05) and had significant diagnostic efficiency (ROC-area under curve of 86%), specificity (72%) and sensitivity (85%) at FFR < 0.8. The corresponding cut-off value for CDP to detect FFR < 0.8 was at CDP>25.4. CDP also correlated significantly (r = 0.98, P < 0.05) with epicardial-specific parameter, HSR. CDP, a functional parameter based on both intracoronary pressure and flow measurements, has close agreement (area under ROC curve = 86%) with FFR, the frequently used method of evaluating stenosis severity.

209 The Development and Validation of anin silicoModel of Coronary Arterial Physiology for Diagnostic Use

<h3>Background</h3> Coronary revascularisation guided by physiological assessment with fractional flow reserve (FFR) improves outcomes and expenditure. However, due to practical limitations, FFR is only used in &lt;10% of percutaneous coronary interventions (PCI) and almost none of the 250,000 diagnostic coronary angiograms performed every year in the UK. We aimed to develop an <i>in silico</i> model of coronary physiology which computes FFR using computational fluid dynamics (CFD) with data from coronary angiography (CAG), which also computes real-time coronary flow. <h3>Methods</h3> We studied 40 patients with stable coronary artery disease undergoing PCI. The <i>in silico</i> workflow reconstructed coronary geometry from CAG images into 3-D geometries using image registration and segmentation protocols. The 3-D domain was coupled to an algebraically encoded zero-D model representing coronary microvascular resistance. CFD simulated pressure and flow. Computed pressures were validated against patient data. Flow was computed from those pressures and validated in a benchtop flow circuit constructed from patient-specific 3-D printed coronary arterial models, a blood analogue, and patient-specific coronary flow patterns using a programmable pump. Pressure and flow were measured with clinical pressure and flow sensitive wires. To reduce computation time, a novel pseudo-transient CFD method was developed and investigated. <h3>Results</h3> Using generic boundary conditions, the initial model computed ‘virtual’ FFR (vFFR) with ±0.06 error and diagnosed physiological lesion significance (FFR &lt;0.80) with 97% accuracy. Ultra-precise, transient CFD took 24 h to compute, whereas the novel ‘pseudo-transient’ method reduced computation to &lt;4 mins on a standard PC with no significant loss of accuracy. Using case-specific boundary conditions (based on invasive measurements) error was reduced to ±0.004 and more useful, artery-specific, patient averaged values yielded ±0.01 error. Coronary flow was computed in all cases and, with the 3-D printed arteries, we demonstrated that the <i>in silico</i> model computed reliable coronary flow with 5.3% error in 3 min. <h3>Conclusions</h3> Our <i>in silico</i> model computes reliable intra-coronary physiology, including pressure and flow, in timescales that are practical for clinical use in the catheter laboratory. Virtual modelling of FFR and hyperaemic stenosis resistance (HSR) is now feasible, which may facilitate increased uptake and impact of physiologically-guided revascularisation planning for every patient undergoing CAG, rather than a small minority undergoing selective PCI. Improved accuracy will follow from better characterisation of the individual’s microvascular resistance. coronary stenosis.