Diagnostic Uncertainties During Assessment of Serial Coronary Stenoses: An In Vitro Study

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Gavin A. D’Souza ◽  
Srikara V. Peelukhana ◽  
Rupak K. Banerjee

Currently, the diagnosis of coronary stenosis is primarily based on the well-established functional diagnostic parameter, fractional flow reserve (FFR: ratio of pressures distal and proximal to a stenosis). The threshold of FFR has a “gray” zone of 0.75–0.80, below which further clinical intervention is recommended. An alternate diagnostic parameter, pressure drop coefficient (CDP: ratio of trans-stenotic pressure drop to the proximal dynamic pressure), developed based on fundamental fluid dynamics principles, has been suggested by our group. Additional serial stenosis, present downstream in a single vessel, reduces the hyperemic flow, Q˜h, and pressure drop, Δp˜, across an upstream stenosis. Such hemodynamic variations may alter the values of FFR and CDP of the upstream stenosis. Thus, in the presence of serial stenoses, there is a need to evaluate the possibility of misinterpretation of FFR and test the efficacy of CDP of individual stenoses. In-vitro experiments simulating physiologic conditions, along with human data, were used to evaluate nine combinations of serial stenoses. Different cases of upstream stenosis (mild: 64% area stenosis (AS) or 40% diameter stenosis (DS); intermediate: 80% AS or 55% DS; and severe: 90% AS or 68% DS) were tested under varying degrees of downstream stenosis (mild, intermediate, and severe). The pressure drop-flow rate characteristics of the serial stenoses combinations were evaluated for determining the effect of the downstream stenosis on the upstream stenosis. In general, Q˜h and Δp˜ across the upstream stenosis decreased when the downstream stenosis severity was increased. The FFR of the upstream mild, intermediate, and severe stenosis increased by a maximum of 3%, 13%, and 19%, respectively, when the downstream stenosis severity increased from mild to severe. The FFR of a stand-alone intermediate stenosis under a clinical setting is reported to be ∼0.72. In the presence of a downstream stenosis, the FFR values of the upstream intermediate stenosis were either within (0.77 for 80%–64% AS and 0.79 for 80%–80% AS) or above (0.88 for 80%–90% AS) the “gray” zone (0.75–0.80). This artificial increase in the FFR value within or above the “gray” zone for an upstream intermediate stenosis when in series with a clinically relevant downstream stenosis could lead to misinterpretation of functional stenosis severity. In contrast, a distinct range of CDP values was observed for each case of upstream stenosis (mild: 8–10; intermediate: 47–54; and severe: 130–155). The nonoverlapping range of CDP could better delineate the effect of the downstream stenosis from the upstream stenosis and allow for the accurate diagnosis of the functional severity of the upstream stenosis.

2013 ◽  
Vol 135 (9) ◽  
Author(s):  
Ishan Goswami ◽  
Srikara V. Peelukhana ◽  
Marwan F. Al-Rjoub ◽  
Lloyd H. Back ◽  
Rupak K. Banerjee

In current practice, diagnostic parameters, such as fractional flow reserve (FFR) and coronary flow reserve (CFR), are used to determine the severity of a coronary artery stenosis. FFR is defined as the ratio of hyperemic pressures distal (p˜rh) and proximal (p˜ah) to a stenosis. CFR is the ratio of flow at hyperemic and basal condition. Another diagnostic parameter suggested by our group is the pressure drop coefficient (CDP). CDP is defined as the ratio of the pressure drop across the stenosis to the upstream dynamic pressure. These parameters are evaluated by invasively measuring flow (CFR), pressure (FFR), or both (CDP) in a diseased artery using guidewire tipped with a sensor. Pathologic state of artery is indicated by lower CFR (<2). Similarly, FFR lower than 0.75 leads to clinical intervention. Cutoff for CDP is under investigation. Diameter and vascular condition influence both flow and pressure drop, and thus, their effect on FFR and CDP was studied. In vitro experiment coupled with pressure-flow relationships from human clinical data was used to simulate pathophysiologic conditions in two representative arterial diameters, 2.5 mm (N1) and 3 mm (N2). With a 0.014 in. (0.35 mm) guidewire inserted, diagnostic parameters were evaluated for mild (∼64% area stenosis (AS)), intermediate (∼80% AS), and severe (∼90% AS) stenosis for both N1 and N2 arteries, and between two conditions, with and without myocardial infarction (MI). Arterial diameter did not influence FFR for clinically relevant cases of mild and intermediate stenosis (difference < 5%). Stenosis severity was underestimated due to higher FFR (mild: ∼9%, intermediate: ∼ 20%, severe: ∼ 30%) for MI condition because of lower pressure drops, and this may affect clinical decision making. CDP varied with diameter (mild: ∼20%, intermediate: ∼24%, severe: by 2.5 times), and vascular condition (mild: ∼35%, intermediate: ∼14%, severe: ∼ 9%). However, nonoverlapping range of CDP allowed better delineation of stenosis severities irrespective of diameter and vascular condition.


Author(s):  
Gavin D’Souza ◽  
Srikara V. Peelukhana ◽  
Rupak K. Banerjee

In patients with multiple stenoses in the same coronary artery, the severity of one stenosis influences the diagnosis of the serial stenosis. Currently used diagnostic end-point, Fractional Flow Reserve, FFR (ratio of distal to proximal pressure of a stenotic region), has a cut-off point of 0.75. A value of FFR < 0.75 leads to a clinical intervention. However, FFR may fail to account for multiple stenoses interactions and might lead to clinical misinterpretation of one serial stenosis severity. In order to assess the effect of one stenosis on the other serial stenosis, we tested three combinations of serial stenoses: 80%–64%, 80%–80% and 80%–90% area stenosis (AS) respectively, using an in-vitro experimental setup. The hyperemic flow decreased from 136.4 ml/min to 126.4 ml/min and further to 90.7 ml/min as downstream stenosis severity increased from 64% AS to 80% AS and further to 90% AS, respectively. More importantly, the individual FFR values of the upstream stenosis (80% AS) increased from 0.76 to 0.79 and further to 0.88 as the downstream stenosis increased from 64% AS to 80% AS and further to 90% AS, respectively. On the contrary, the combined FFR across both the stenosis was below the threshold value of 0.75. These results indicate that the presence of a downstream stenosis might lead to a clinical misinterpretation of the upstream stenosis severity and also the combined stenosis severity.


Author(s):  
Kranthi K. Kolli ◽  
Mohamed Effat ◽  
Imran Arif ◽  
Tarek Helmy ◽  
Massoud Leesar ◽  
...  

Fractional flow reserve (FFR: ratio of distal to proximal pressure of a stenotic section) is used to evaluate hemodynamic significance of epicardial stenosis. However, FFR and coronary flow reserve (CFR: ratio of hyperemic blood velocity to that of resting condition) are used in conjunction to evaluate combination of both epicardial and microvascular disease. It has been proposed that optimization of cutoff values for diagnostic parameters in determining stenosis severity depends on coupling functional (pressure and velocity) and anatomical data (% area stenosis). We hypothesize that, pressure drop coefficient (CDP: the ratio of trans-stenotic pressure drop to distal dynamic pressure) which has the functional information of pressure and velocity in its formulation correlates significantly with FFR and CFR, and lesion flow coefficient (LFC: ratio of % area stenoses to CDP at throat region) which combines both functional and anatomical (% area stenoses) information in its formulation correlates significantly with FFR, CFR and % area stenosis. We retrospectively analyzed the hemodynamic information from Meuwissen et al [3] to test this hypothesis. It was observed that, CDP, a functional index based on pressure drop and velocity, correlated linearly and significantly with FFR and CFR. And, LFC (combined functional and anatomic parameter) also correlated significantly with FFR, CFR (both hemodynamic endpoints) and % area stenosis (anatomic endpoint).


Author(s):  
Gavin A. D’Souza ◽  
Srikara V. Peelukhana ◽  
Rupak K. Banerjee

Diagnosis of the functional severity of an epicardial coronary stenosis using parameters like Fractional Flow Reserve, FFR (ratio of distal to proximal pressure of a stenotic region), might be affected in the presence of an additional downstream stenosis. In order to assess this effect, we have performed an in-vitro experiment which is used to validate a computational study. Three combinations of serial stenoses were tested: 80%-64%, 80%-80% and 80%-90% area stenosis (AS). The physiological mean hyperemic flow (flow at maximal arterial dilatation) values were obtained using an in-vitro experimental set-up. These flow rates were used as steady flow inputs by time-averaging the spatially averaged flow pulse over two cardiac cycles for the computational study. FFR values were calculated at hyperemic flow using both the experimental and numerical pressure data. As the downstream severity increased from 64% AS to 80% AS, hyperemic coronary flow decreased from 136.4 ml/min to 126.4 ml/min. Flow decreased further to 90.7 ml/min with a downstream severity of 90% AS. FFR of the intermediate stenosis increased from 0.76 to 0.79 and further to 0.88 as the downstream stenosis increased from 64% to 80% with a final severity of 90% AS. Similarly, numerically obtained FFR values increased to 0.83, 0.80 and 0.92 for the corresponding cases indicating an error within 7% of the experimental values. These results indicate that the presence of a downstream stenosis might lead to a clinical misinterpretation of the upstream stenosis severity.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Soohong Min ◽  
Gwansuk Kang ◽  
Dong-Guk Paeng ◽  
Joon Hyouk Choi

Abstract Background and objectives Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are the two most commonly used coronary indices of physiological stenosis severity based on pressure. To minimize the effect of wedge pressure (Pwedge), FFR is measured during hyperemia conditions, and iFR is calculated as the ratio of distal and aortic pressures (Pd/Pa) in the wave-free period. The goal of this study was to predict Pwedge using the backward wave (Pback) through wave separation analysis (WSA) and to reflect the effect of Pwedge on FFR and iFR to identify the relationship between the two indices. Methods An in vitro circulation system was constructed to calculate Pwedge. The measurements were performed in cases with stenosis percentages of 48, 71, and 88% and with hydrostatic pressures of 10 and 30 mmHg. Then, the correlation between Pback by WSA and Pwedge was calculated. In vivo coronary flow and pressure were simultaneously measured for 11 vessels in all patients. The FFR and iFR values were reconstructed as the ratios of forward wave at distal and proximal sites during hyperemia and at rest, respectively. Results Based on the in vitro results, the correlation between Pback and Pwedge was high (r = 0.990, p < 0.0001). In vivo results showed high correlations between FFR and reconstructed FFR (r = 0.992, p < 0.001) and between iFR and reconstructed iFR (r = 0.930, p < 0.001). Conclusions Reconstructed FFR and iFR were in good agreement with conventional FFR and iFR. FFR and iFR can be expressed as the variation of trans-stenotic forward pressure, indicating that the two values are inferred from the same formula under different conditions.


Author(s):  
Kranthi K. Kolli ◽  
Mohamed Effat ◽  
Tarek Helmy ◽  
Massoud Leesar ◽  
Arif Imran ◽  
...  

Invasive guide-wire measurements are used to assess coronary lesion severity under clinical settings. The objective of the present research is to determine the influence of heart rate (HR) and contractility (CY) on fractional flow reserve (FFR; the ratio of distal pressure to proximal pressure at a stenotic section) and pressure drop coefficient (CDPe; the ratio of trans-stenotic pressure drop to distal dynamic pressure). In-vivo experiments were performed on eight Yorkshire pigs, to evaluate the diagnostic parameters for the conditions “CY<1100 mmHg/sec” and “CY>1100 mmHg/sec,” and for the conditions “HR<110 bpm” and “HR>110 bpm”. It was found that in the presence of normal microvasculature the measured coronary diagnostic parameters (FFR and CDPe) have a significant mean difference for variation in contractility (0.59±0.04 to 0.89±0.045 for FFR and 121.63±18 to 23.53±18 for CDPe). The variation in HR has no significant effect on FFR and CDPe (0.72±0.048 to 0.74±0.048 and 54±20 to 53±20 respectively).


Author(s):  
Ishan Goswami ◽  
Srikara V. Peelukhana ◽  
Marwan Al-Rjoub ◽  
Lloyd H. Back ◽  
Rupak K. Banerjee

Fractional flow reserve (FFR), the ratio of the pressures distal (Pd) and proximal (Pa) to a stenosis, and coronary flow reserve (CFR), the ratio of flows at maximal vasodilation to the resting condition, are widely used for determining the functional severity of a coronary artery stenosis. However, the diameter of the native artery might influence the FFR values. Therefore, using an in-vitro experimental study, we tested the variation of FFR for two arterial diameters, 2.5 mm (N1) and 3 mm (N2). We hypothesize that FFR is not influenced by native arterial diameter. For both N1 and N2, vasodilation-distal perfusion pressure (CFR-Prh) curves were obtained using a 0.35 mm guidewire by simulating physiologic flows under different blockage conditions: mild (64% area stenosis (AS)), intermediate (80% AS) and severe (90% AS). The FFR values for the two arterial models differed insignificantly, within 3%, for mild and intermediate stenoses but differed appreciably for severe stenosis (∼25%). This significant difference in FFR values for severe stenosis can be attributed to relatively larger difference in guidewire obstruction effect at the stenotic throat region of the two native arterial models. These findings confirm that FFR will not differ for the clinically relevant cases of mild and intermediate stenosis for different arterial diameters.


Author(s):  
Kranthi K. Kolli ◽  
Mohamed Effat ◽  
Imran Arif ◽  
Tarek Helmy ◽  
Massoud Leesar ◽  
...  

Optimization of cut-off values for diagnostic parameters in determining stenosis severity depends on coupling functional (hemodynamic) and anatomical data. In this study, we sought to investigate the functional diagnostic parameter (CDP; the ratio of trans-stenotic pressure drop to distal dynamic pressure) by correlating with FFR (ratio of distal to proximal pressure of a stenotic section) and CFR (ratio of hyperemic blood flow velocity to that of resting condition). A 0.014-inch dual sensor (pressure and Doppler velocity) guidewire was used in 9 patients to obtain pressure drop and velocity at hyperemia. Functional index CDP was assessed from measured hyperemic pressure drop and velocity. CDP correlated linearly and significantly with FFR and CFR. Indicating that, measurements of CDP can provide a better assessment of stenosis severity.


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