Eric W. Schneeberger

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.

Functional and anatomical diagnosis of coronary artery stenoses.

BACKGROUND Functional/physiological evaluation of coronary artery stenoses may be more important than anatomical measurements of severity. Optimization of thresholds for stenosis intervention and treatment endpoints depend on coupling functional hemodynamic and anatomical data. We sought to develop a single prognostic parameter correlating stenosis-specific anatomy, pressure gradient, and velocities that could be measured during catheterization. MATERIALS AND METHODS In vivo Experiments were performed in six swine (41 +/- 3 kg). The lumen area of the left anterior descending coronary artery was measured with intravascular ultrasound. An angioplasty balloon was inflated to create the desired intraluminal area obstructions. Fractional flow reserve (FFR), coronary flow reserve (CFR), and hyperemic-stenosis-resistance index were measured distal to the balloon at peak hyperemia with 10 mg intracoronary papaverine. A functional index:pressure drop coefficient (CDP) and a combined functional and anatomical index:lesion flow coefficient (LFC) were calculated from measured hyperemic pressure gradient, velocity, and percentage area stenosis. P < 0.05 was considered statistically significant. RESULTS The CDP and LFC correlated linearly and significantly with FFR and CFR. The CDP (R(2) = 0.72, P < 0.0001) correlated better than LFC (R(2) = 0.19, P < 0.003) with hyperemic-stenosis-resistance index. When LFC was correlated simultaneously with FFR and CFR, R(2) improved to 0.82 (P < 0.0001). Inclusion of percentage area stenoses concurrently with FFR and CFR marginally improved the correlation with LFC. CONCLUSIONS A dimensionless parameter combining measured pressure gradient, velocity, and area reduction data can optimally define the severity of coronary stenoses based on our preliminary results and could prove useful clinically.

Effect of heart rate on hemodynamic endpoints under concomitant microvascular disease in a porcine model

Diagnosis of the ischemic power of epicardial stenosis with concomitant microvascular disease (MVD) is challenging during coronary interventions, especially under variable hemodynamic factors like heart rate (HR). The goal of this study is to assess the influence of variable HR and percent area stenosis (%AS) in the presence of MVD on pressure drop coefficient (CDP; ratio of transstenotic pressure drop to the distal dynamic pressure) and lesion flow coefficient (LFC; ratio of %AS to the CDP at the throat region). We hypothesize that CDP and LFC are independent of HR. %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop (DP) and velocity were done in 11 Yorkshire pigs. Fractional flow reserve (FFR), CDP, and LFC were calculated for the groups HR < 120 and HR > 120 beats/min, %AS < 50 and %AS > 50, and additionally for DP < 14 and DP > 14 mmHg, and analyzed using regression and ANOVA analysis. Regression analysis showed independence between HR and the FFR, CDP, and LFC while it showed dependence between %AS and the FFR, CDP, and LFC. In the ANOVA analysis, for the HR < 120 beats/min and HR > 120 beats/min groups, the values of FFR (0.82 ± 0.02 and 0.82 ± 0.02), CDP (83.15 ± 26.19 and 98.62 ± 26.04), and LFC (0.16 ± 0.03 and 0.15 ± 0.03) were not significantly different (P > 0.05). However, for %AS < 50 and %AS > 50, the FFR (0.89 ± 0.02 and 0.75 ± 0.02), CDP (35.97 ± 25.79.10 and 143.80 ± 25.41), and LFC (0.09 ± 0.03 and 0.22 ± 0.03) were significantly different (P < 0.05). A similar trend was observed between the DP groups. Under MVD conditions, FFR, CDP, and LFC were not significantly influenced by changes in HR, while they can significantly distinguish %AS and DP groups.

Effect of myocardial contractility on hemodynamic end points under concomitant microvascular disease in a porcine model

In this study, coronary diagnostic parameters, pressure drop coefficient (CDP: ratio of trans-stenotic pressure drop to distal dynamic pressure), and lesion flow coefficient (LFC: ratio of % area stenosis (%AS) to the CDP at throat region), were evaluated to distinguish levels of %AS under varying contractility conditions, in the presence of microvascular disease (MVD). In 10 pigs, %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop, left ventricular pressure (p), and velocity were obtained. Contractility was calculated as (dp/dt)max, categorized into low contractility <900 mmHg/s and high contractility >900 mmHg/s, and in each group, compared between %AS <50 and >50 using analysis of variance. In the presence of MVD, between the %AS <50 and >50 groups, values of CDP (71 ± 1.4 and 121 ± 1.3) and LFC (0.10 ± 0.04 and 0.19 ± 0.04) were significantly different (P < 0.05), under low-contractility conditions. A similar %AS trend was observed under high-contractility conditions (CDP: 18 ± 1.4 and 91 ± 1.4; LFC: 0.08 ± 0.04 and 0.25 ± 0.04). Under MVD conditions, similar to fractional flow reserve, CDP and LFC were not influenced by contractility.

A rare case of Klebsiella pneumoniae myocardial abscess

Myocardial abscess of the left ventricular free wall in the absence of infective endocarditis (IE) is very unusual. Most cases are discovered during autopsies and are due to Gram-positive cocci. We present a rare case of Klebsiella pneumoniae causing myocardial abscess of the left ventricular free wall. The patient had no evidence of valvular endocarditis or bacteremia, and the abscess was discovered during coronary artery bypass grafting surgery (CABG).

Distinguishing Epicardial and Microvascular Disease Using Combined Functional and Anatomical Endpoints in a Porcine Model

For a better treatment of coronary artery disease in a catheterization lab, detection of the relative contributions of the epicardial stenosis (ES) and concomitant microvascular disease (MVD) is important. To diagnose ES, fractional flow reserve (FFR), the hyperemic stenosis resistance index (hSRv) and to diagnose MVD, hyperemic microvascular resistance index (hMRv) have been tested in cath labs. However, for concurrent assessment of ES and MVD, functional parameter utilizing flow and pressure values, pressure drop coefficient (CDP) and combined functional and anatomical parameter, lesion flow coefficient (LFC) are defined. To test the ability of CDP and LFC to account for ES and MVD, they were correlated with the hSRv and hMRv. We hypothesize that CDP and LFC will have a better combined correlation with hSRv and hMRv.Simultaneous pressure and flow readings were obtained in 11 Yorkshire swine. Single and multiple linear regression analyses were conducted between the FFR, CDP and LFC vs hSRv and hMRv. The correlation coefficient (r) was used to check the strength of correlation.The individual correlation between hSRv and hMRV with CDP (r = 0.90; r = 0.78) and LFC (r = 0.89; r = 0.95) was stronger compared to FFR (r = 0.63; r = 0.32). The combined correlation between hSRv and hMRv with CDP (r = 0.95) and LFC (r = 0.95) increased from the individual correlation. Therefore, we conclude that CDP and LFC can diagnose ES and MVD concurrently and might prove to be improved diagnostic parameters than FFR.Copyright

INFLUENCE OF HEART RATE AND EPICARDIAL STENOSIS SEVERITY ON CARDIAC CONTRACTILITY UNDER CONCOMITANT MICROVASCULAR DISEASE IN A PORCINE MODEL

Invasive guide wire methods to assess functional severity of coronary stenosis are affected by dynamic variables like heart rate (HR), contractility, epicardial stenosis (AS) and blood pressure. The interdependence of these factors is also influenced by the presence of concomitant microvascular disease (CMVD). The purpose of this study is to assess the variation in contractility under varying HR and AS in the presence of CMVD. In vivo experiments were performed on seven Yorkshire pigs. It was found that, in the presence of concomitant microvascular disease (CMVD), for lower AS ( 120 bpm. However, for higher AS (>50%), contractility decreases for both HR 120 bpm.Copyright

INFLUENCE OF HEART RATE AND CONTRACTILITY ON CORONARY DIAGNOSTIC PARAMETERS WITH NORMAL MICROVASCULATURE IN PORCINE MODEL

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 for the conditions “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 to0.89±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 to53±20 respectively).

INFLUENCE OF HEART RATE AND AREA STENOSIS ON CORONARY DIAGNOSTIC PARAMETERS IN A PORCINE MODEL

Several parameters have been proposed to assess the physiologic significance of coronary lesions invasively. The purpose of the present study is to determine the effect of heart rate and percentage area stenosis on Fractional Flow Reserve (FFR), which is the ratio of mean pressure distal to stenosis over the mean proximal (aortic) pressure and Pressure Drop Coefficient (CDP), ratio of trans-stenotic pressure gradient to distal dynamic pressure. In-vivo experiments were performed on three Yorkshire pigs, to achieve the objective. It was found that increase in heart rate does have a significant effect on the coronary diagnostic parameters with increase in area stenosis.Copyright