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.

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.

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.

Effect of higher frequency components and duration of vibration on bone tissue alterations in the rat-tail model.

To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under different frequencies and duration of vibration needs elucidation. Rat-tails were vibrated at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s(2), for 1D (6 rats), 5D (6 rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being subjected to any vibration. Structural and biochemical damages were quantified using empty lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure mixed-model ANOVA at p<0.05 level of significance was used for analysis. In the cortical bone, structural damage quantified through empty lacunae count was significant (p<0.05) at 250 Hz (10.82 ± 0.66) in comparison to the control group (7.41 ± 0.76). The biochemical damage was significant (p<0.05) at both the 125 Hz and 250 Hz vibration frequencies. The structural damage was significant (p<0.05) at 5D for cortical bone while the trabecular bone showed significant (p<0.05) damage at 20D time point. Further, the biochemical damage increased with increase in the duration of vibration with a significant (p<0.05) damage observed at 20D time point and a near significant change (p=0.08) observed at 5D time point. Structural and biochemical changes in bone tissue are dependent upon higher vibration frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D).

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.

Benefit of cardiac N-13 PET CFR for combined anatomical and functional diagnosis of ischemic coronary artery disease: a pilot study.

BACKGROUND: Cardiac positron emission tomography (PET) can lead to flow impairment quantification using PET coronary flow reserve (CFRp: ratio of stress flow to rest flow) and is superior to the current standard, single-photon emission computed tomography. In this study, our first aim was to assess the benefit of CFRp in place of invasive CFR (CFRi) by comparing the correlations of each of the indices with combined pressure and flow index CDP, and combined functional (pressure-flow) and anatomical (%area stenosis, %AS) index, LFC. The second aim was to test the correlation between CFRp and CFRi. METHODS: N-13 ammonia PET scans were performed and CFRp was obtained using a 1-compartment 2K-dynamic volume (DV)-constant kinetic model in Flowquant. During catheterization, simultaneous pressure and flow readings were obtained in 10 vessels (three vessels in one patient, one vessel each in 7 patients) using a dual sensor tipped Combowire, and CFRi, CDP, LFC, and FFR were computed. %AS was obtained using quantitative coronary angiography. CDP was correlated with invasive pressure index (FFR) and CFRp and with FFR and CFRi. LFC was correlated with the %AS, FFR, and CFRp/CFRi, individually and in combination. Correlation analysis was done in SAS; p < 0.05 was used for statistical significance. RESULTS: The correlations between CDP vs FFR and CFRp (r = 0.62, p = 0.19) in combination, as well as CDP vs FFR and CFRi in combination (r = 0.58, p = 0.24) remained similar. The correlation between LFC vs FFR, CFRp and %AS in combination improved (r = 0.82) with a near-significant p = 0.06, in comparison to the correlation between LFC vs FFR, CFRi and %AS in combination (r = 0.75, p = 0.15). CFRp correlated strongly and significantly (r = 0.82, p = 0.003) with CFRi, and the values were within 11 %. CONCLUSION: The novelty of the PET procedure in this study is that the noninvasive CFRp can be used instead of invasive CFRi for the functional diagnosis of CAD. Therefore, a PET scan can reduce procedure time and cost while simplifying the diagnostic protocol for assessing coronary artery disease, thus benefitting both the patients and clinicians.

Hyperemia-free delineation of epicardial and microvascular impairments using a basal index.

The assessment of functional coronary lesion severity using intracoronary hemodynamic parameters like the pressure-derived fractional flow reserve and the flow-derived coronary flow reserve are known to rely critically on the establishment of maximal hyperemia. We evaluated a hyperemia-free index, basal pressure drop coefficient (bCDP), that combines pressure and velocity for simultaneous assessment of the status of both epicardial and microvascular circulations. In 23 pigs, simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual-sensor tipped guidewire in the settings of both normal and abnormal microcirculation with the presence of epicardial lesions of area stenosis (AS) < 50% and AS > 50%. The bCDP, a parameter based on fundamental fluid dynamics principles, was calculated as the transtenotic pressure-drop divided by the dynamic pressure in the distal vessel, measured under baseline (without hyperemia) conditions. The group mean values of bCDP for normal (84 ± 18) and abnormal (124.5 ± 15.6) microcirculation were significantly different. Similarly, the mean values of bCDP from AS < 50% (72.5 ± 16.1) and AS > 50% (136 ± 17.2) were also significantly different (p < 0.05). The bCDP could significantly distinguish between lesions of AS < 50% to AS > 50% under normal microcirculation (52.1 vs. 85.8; p < 0.05) and abnormal microcirculation (84.9 vs. 172; p < 0.05). Further, the bCDP correlated linearly and significantly with the hyperemic parameters FFR (r = 0.42, p < 0.05) and CDP (r = 0.50, p < 0.05). The bCDP is a promising clinical diagnostic parameter that can independently assess the severity of epicardial stenosis and microvascular impairment. We believe that it has an immediate appeal for detection of coronary artery disease if validated clinically.

Diagnostic performance of pressure drop coefficient in relation to fractional flow reserve and coronary flow reserve.

OBJECTIVES AND BACKGROUND: Functional assessment of coronary lesion severity during cardiac catheterization is conducted using diagnostic parameters like fractional flow reserve (FFR; pressure derived) and coronary flow reserve (CFR; flow derived). However, the complex hemodynamics of stenosis might not be sufficiently explained by either pressure or flow alone, particularly in the case of intermediate stenosis. CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a non-dimensional index derived from fundamental fluid dynamic principles based on a combination of intracoronary pressure and flow, may improve the functional assessment of coronary lesion severity. METHODS: We performed a meta-analysis of seven studies, retrieved from MEDLINE and PubMed, comparing the results of FFR and CFR of the same lesions. Two studies reported functional measurements (pressure and flow) obtained in individual patients. Five studies reported two-dimensional plots of FFR vs. CFR. The FFR and CFR data were digitized and corresponding functional measurements were extracted using the reported mean values of hemodynamic data from each of the five studies. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off point of CDP, which corresponds to the clinically used cut-off values (FFR = 0.80, FFR = 0.75, and CFR = 2.0). RESULTS: CDP correlated significantly with FFR (r = 0.78; P<.001) and had significant diagnostic efficiency (area under the ROC curve = 89%), specificity (83% and 85%), and sensitivity (81% and 76%) at FFR <0.8 and FFR <0.75, respectively. The corresponding cut-off value for CDP to detect FFR <0.80 and FFR <0.75 was at CDP >27.1 and CDP >27.9, respectively. CONCLUSIONS: CDP, a functional parameter based on both intracoronary pressure and flow measurements, has close agreement (area under the ROC curve = 89%) with FFR, the most frequently used method for evaluation of coronary stenosis severity.

Influence of newly designed monorail pressure sensor catheter on coronary diagnostic parameters: an in vitro study.

The decision to perform intervention on a patient with coronary stenosis is often based on functional diagnostic parameters obtained from pressure and flow measurements using sensor-tipped guidewire at maximal vasodilation (hyperemia). Recently, a rapid exchange Monorail Pressure Sensor catheter of 0.022″ diameter (MPS22), with pressure sensor at distal end has been developed for improved assessment of stenosis severity. The hollow shaft of the MPS22 is designed to slide over any standard 0.014″ guidewire (G14). Hence, influence of MPS22 diameter on coronary diagnostic parameters needs investigation. An in vitro experiment was conducted to replicate physiologic flows in three representative area stenosis (AS): mild (64% AS), intermediate (80% AS), and severe (90% AS), for two arterial diameters, 3mm (N2; more common) and 2.5mm (N1). Influence of MPS22 on diagnostic parameters: fractional flow reserve (FFR) and pressure drop coefficient (CDP) was evaluated both at hyperemic and basal conditions, while comparing it with G14. The FFR values decreased for the MPS22 in comparison to G14, (Mild: 0.87 vs 0.88, Intermediate: 0.68 vs 0.73, Severe: 0.48 vs 0.56) and CDP values increased (Mild: 16 vs 14, Intermediate: 75 vs 56, Severe: 370 vs 182) for N2. Similar trend was observed in the case of N1. The FFR values were found to be well above (mild) and below (intermediate and severe) the diagnostic cut-off of 0.75. Therefore, MPS22 catheter can be used as a possible alternative to G14. Further, irrespective of the MPS22 or G14, basal FFR (FFRb) had overlapping ranges in close proximity for clinically relevant mild and intermediate stenoses that will lead to diagnostic uncertainty under both N1 and N2. However, CDPb had distinct ranges for different stenosis severities and could be a potential diagnostic parameter under basal conditions.

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.

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.

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.

Dependence of vascular damage on higher frequency components in the rat-tail model.

Hand-Arm Vibration Syndrome (HAVS) is caused by hand-transmitted vibration in industrial workers. Current ISO guidelines (ISO 5349) might underestimate vascular injury associated with range of vibration frequencies near resonance. A rat-tail model was used to investigate the effects of higher frequencies >100 Hz on early vascular damage. 13 Male Sprague-Dawley rats (250 ± 15 gm) were used. Rat-tails were vibrated at 125 Hz and 250 Hz (49 m/s(2)) for 1D, 5D and 10D; D=days (4 h/day). Structural damage of the ventral artery was quantified by vacuole count using Toluidine blue staining whereas biochemical changes were assessed by nitrotyrosine (NT) staining. The results were analyzed using one-way repeated measures mixed-model ANOVA at p<0.05 level of significance. The structural damage increased at 125 Hz causing significant number of vacuoles (40.62 ± 9.8) compared to control group (8.36 ± 2.49) and reduced at 250 Hz (12.33 ± 2.98) compared to control group (8.36 ± 2.49). However, the biochemical alterations (NT-signal) increased significantly for 125 Hz (143.35 ± 5.8 gray scale value, GSV) and for 250 Hz (155.8 ± 7.35 GSV) compared to the control group (101.7 ± 4.18 GSV). Our results demonstrate that vascular damage in the form of structural and bio chemical disruption is significant at 125 Hz and 250 Hz. Hence the current ISO guidelines might underestimate vascular damage at frequencies>100 Hz.

Effect of changes in contractility on pressure drop coefficient and fractional flow reserve in a porcine model.

OBJECTIVES AND BACKGROUND: Decisions based on invasive functional diagnostic measurements are often made in the setting of fluctuating hemodynamic variables that may alter resting or hyperemic measurements. The purpose of this investigation is to analyze the effect of myocardial contractility (CY) on invasive functional parameters. We hypothesize that the pressure drop coefficient (CDPe; ratio of pressure drop to distal dynamic pressure) and fractional flow reserve (FFR; ratio of average pressures distal and proximal to a stenosis) are not affected by fluctuations in CY and can distinguish between different severities of epicardial stenosis. METHODS: Simultaneous measurements of distal coronary-arterial pressure and velocity were performed in 10 pigs using a dual-sensor tipped guidewire for heart rate (HR) <110 bpm and HR >110 bpm, in the presence of coronary lesions of <50% area stenosis (AS) and >50% AS. Variations in myocardial function and vascular resistance were induced by atrial pacing, papaverine and balloon obstruction, respectively. The maximum rate of rise of left ventricular pressure ([dp/dt]max) was the index of contractility. The contractile function of the heart was empirically defined as CY >900 mm Hg/sec (higher) and CY <900 mm Hg/sec (normal). RESULTS: For CY >900 mm Hg/sec, under AS <50% and AS >50%, the mean values of FFR (0.91 ± 0.02 and 0.78 ± 0.02), and CDPe (15.6 ± 5.3 and 70.7 ± 24.7) were significantly different (P<.05). Similarly, for CY <900 mm Hg/sec, under AS <50% and AS >50%, the mean values of FFR (0.83 ± 0.04 and 0.63 ± 0.04), and CDPe (43.8 ± 14.9 and 191.8 ± 61.4) were also significantly different (P<.05). CONCLUSIONS: Both FFR and CDPe could effectively distinguish between stenosis severity at normal and higher levels of myocardial contractility.

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.