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

OBJECTIVES AND BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Functional diagnosis of coronary stenoses using pressure drop coefficient: a pilot study in humans.

OBJECTIVES AND BACKGROUND: Myocardial fractional flow reserve (FFR) in conjunction with coronary flow reserve (CFR) is used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between FFR and CFR have been observed in intermediate coronary lesions. A functional parameter, pressure drop coefficient (CDP; ratio of pressure drop to distal dynamic pressure), was assessed using intracoronary pressure drop (dp) and average peak velocity (APV). The CDP is a nondimensional ratio, derived from fundamental fluid dynamic principles. We sought to evaluate the correlation of CDP with FFR, CFR, and hyperemic stenosis resistance (HSR: ratio of pressure drop to APV) in human subjects. METHODS: Twenty-seven patients with reversible perfusion defects based on SPECT were consented for the study before cardiac catheterization. Distal coronary pressure and APV were measured simultaneously for each coronary lesion using a Combowire(©) during cardiac catheterization. Reference diameter, minimal lumen diameter, and %AS were obtained by quantitative coronary angiography. Maximum hyperemia was induced by IV adenosine (140 µg/kg/min). CDP was calculated as, (Δp)/(0.5 × ρ × APV(2) ). The density of blood (ρ) was assumed to be 1.05 gm/cm(3) . RESULTS: The functional index, CDP, when correlated simultaneously with FFR and CFR, was found to have a significant correlation (r = 0.61; P < 0.05). Similarly a significant correlation was achieved when CDP was correlated with HSR (r = 0.91; P < 0.001). This is consistent with the definition of CDP, which is a functional parameter that includes both pressure and flow information. CONCLUSIONS: CDP, a nondimensional parameter combining simultaneous measurements of pressure drop and velocity data, can accurately define the severity of coronary stenoses and could prove advantageous clinically.

Diagnostic uncertainties during assessment of serial coronary stenoses: an in vitro study.

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.

Influence of variable native arterial diameter and vasculature status on coronary diagnostic parameters.

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.

Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model.

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.

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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: LFC, a parameter that combines both the anatomical and functional end-points, has the potential for application in a clinical setting for CAD evaluation.

Delineation of epicardial stenosis in patients with microvascular disease using pressure drop coefficient: A pilot outcome study.

AIM: To investigate the patient-outcomes of newly developed pressure drop coefficient (CDP) in diagnosing epicardial stenosis (ES) in the presence of concomitant microvascular disease (MVD). METHODS: Patients from our clinical trial were divided into two subgroups with: (1) cut-off of coronary flow reserve (CFR) < 2.0; and (2) diabetes. First, correlations were performed for both subgroups between CDP and hyperemic microvascular resistance (HMR), a diagnostic parameter for assessing the severity of MVD. Linear regression analysis was used for these correlations. Further, in each of the subgroups, comparisons were made between fractional flow reserve (FFR) < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events (MACE: Primary outcome). Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups. Two tailed chi-squared and Fischer's exact tests were performed for comparison of the primary outcomes, and the log-rank test was used to compare the Kaplan-Meier survival curves. P < 0.05 for all tests was considered statistically significant. RESULTS: Significant linear correlations were observed between CDP and HMR for both CFR < 2.0 (r = 0.58, P < 0.001) and diabetic (r = 0.61, P < 0.001) patients. In the CFR < 2.0 subgroup, the %MACE (primary outcomes) for CDP > 27.9 group (7.7%, 2/26) was lower than FFR < 0.75 group (3/14, 21.4%); P = 0.21. Similarly, in the diabetic subgroup, the %MACE for CDP > 27.9 group (12.5%, 2/16) was lower than FFR < 0.75 group (18.2%, 2/11); P = 0.69. Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group (n = 26) when compared with FFR < 0.75 group (n = 14); P = 0.10. Similarly, for the diabetic subgroup, CDP > 27.9 group (n = 16) showed higher survival times compared to FFR group (n = 11); P = 0.58. CONCLUSION: CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR. These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.

Role of Pulse Pressure and Geometry of Primary Entry Tear in Acute Type B Dissection Propagation.

The hemodynamic and geometric factors leading to propagation of acute Type B dissections are poorly understood. The objective is to elucidate whether geometric and hemodynamic parameters increase the predilection for aortic dissection propagation. A pulse duplicator set-up was used on porcine aorta with a single entry tear. Mean pressures of 100 and 180 mmHg were used, with pulse pressures ranging from 40 to 200 mmHg. The propagation for varying geometric conditions (%circumference of the entry tear: 15-65%, axial length: 0.5-3.2 cm) were tested for two flap thicknesses (1/3rd and 2/3rd of the thickness of vessel wall, respectively). To assess the effect of pulse and mean pressure on flap dynamics, the %true lumen (TL) cross-sectional area of the entry tear were compared. The % circumference for propagation of thin flap (47 ± 1%) was not significantly different (p = 0.14) from thick flap (44 ± 2%). On the contrary, the axial length of propagation for thin flap (2.57 ± 0.15 cm) was significantly different (p < 0.05) from the thick flap (1.56 ± 0.10 cm). TL compression was observed during systolic phase. For a fixed geometry of entry tear (%circumference = 39 ± 2%; axial length = 1.43 ± 0.13 cm), mean pressure did not have significant (p = 0.84) effect on flap movement. Increase in pulse pressure resulted in a significant change (p = 0.02) in %TL area (52 ± 4%). The energy acting on the false lumen immediately before propagation was calculated as 75 ± 9 J/m2 and was fairly uniform across different specimens. Pulse pressure had a significant effect on the flap movement in contrast to mean pressure. Hence, mitigation of pulse pressure and restriction of flap movement may be beneficial in patients with type B acute dissections.

Benefit of ECG-gated rest and stress N-13 cardiac PET imaging for quantification of LVEF in ischemic patients.

BACKGROUND: ECG-gated rest-stress cardiac PET can lead to simultaneous quantification of both left ventricular ejection fraction and flow impairment. In this study, our aim was to assess the benefit of rest and stress PET ejection fraction (EF) (EFp) in relation to single-photon emission computed tomography (SPECT) EF (EFs) and echocardiography EF (EFe). To this effect, the EFp was compared with EFs and EFe. Further, the relation between rest and stress EFp was also assessed. METHODS: ECG-gated N-13 ammonia rest and stress PET imaging was performed in 26 patients. EFp values were obtained using gated reconstruction of the data in Flowquant. In 13 patients, EFs and EFe values were obtained through chart review. Correlation, analysis of variance, and Bland-Altman analyses were performed. P values less than 0.05 were used for statistical significance. RESULTS: The rest and stress EFp values correlated significantly (r=0.80 and 0.71, respectively; P<0.05) with EFs values. There was moderate correlation with statistical significance (P<0.05) between the rest and stress EFp and EFe values (r=0.58 and 0.50, respectively). The mean rest and stress EFp values were not significantly different from mean EFs values. Also, the rest EFp and stress EFp values correlated well (r=0.81, P<0.05) and were not significantly different. Bland-Altman analysis showed no significant bias between the rest and stress EFp, and EFs, and EFe values. CONCLUSION: Rest and stress EFp values obtained through an ECG-gated PET scan can be used for clinical diagnosis in place of conventional methods like SPECT and echocardiography.

Lesion flow coefficient: a combined anatomical and functional parameter for detection of coronary artery disease--a clinical study.

Invasive diagnosis of coronary artery disease utilizes either anatomical or functional measurements. In this study, we tested a futuristic parameter, lesion flow coefficient (LFC, defined as the ratio of percent coronary 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) for application in a clinical setting. In 51 vessels, simultaneous pressure and flow readings were obtained using a 0.014" Combowire (Volcano Corporation). Anatomical details were assessed using quantitative coronary angiography (QCA). Fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR), and hyperemic microvascular index (HMR) were obtained at baseline and adenosine-induced hyperemia. QCA data were corrected for the presence of guidewire and then the LFC values were calculated. LFC was correlated with FFR, CFR, HSR, and HMR, individually and in combination with %AS, under both baseline and hyperemic conditions. Further, in 5 vessels, LFC group mean values were compared between pre-PCI and post-PCI groups. P<.05 was considered statistically significant. LFC measured at hyperemia correlated significantly when the pressure-based FFR, flow-based CFR, and anatomically measured %AS were combined (r = 0.64; P<.05). Similarly, LFC correlated significantly when HSR, HMR, and %AS were combined (r = 0.72; P<.05). LFC was able to significantly distinguish between pre-PCI and post-PCI groups (0.42 ± 0.05 and 0.05 ± 0.004, respectively; P<.05). Similar results were obtained for the LFC at baseline conditions. LFC, a futuristic parameter that combines both the anatomical and functional endpoints, has potential for application in a clinical setting for stenosis evaluation, under both hyperemic and baseline conditions.