Functional assessment of coronary artery stenoses using coronary artery pressure wires is an important diagnostic tool in the catheterization laboratory. Fractional flow reserve (FFR) is calculated as the ratio of distal intracoronary pressure to the proximal intracoronary pressure during pharmacologically induced hyperemia [
This study protocol was approved by the ethics committee at our institution and conducted in accordance with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all patients.
Patients who were suspected of having ischemic heart disease and underwent cardiac computed tomography (CT) with confirmed stenosis were prospectively enrolled from September 2017 to November 2018. Patients with acute coronary syndromes, those who did not undergo cardiac CT, and those whose puncture sites were not radial arteries were excluded. Patients with pressure wires that were difficult to manipulate due to tortuous vessels in the supine position did not undergo another measurement in the prone position, as judged by the operator.
Approach sites were the right or left radial arteries. Catheter examinations were performed using 4-French catheters (Goodtec JR4, JR (right radial), JL3.5, JL4, Goodman, Japan) after 3000-U heparin administration. The fourth intercostal axillary midline, which is the height of the right atrium, was taken as the zero point of the blood pressure line. The first cardiac catheterization was performed in the supine position. The pressure transducer was placed on the catheterization table level. A 0.014-inch pressure sensor-tipped wire (PressureWire™ X, St. Jude Medical, USA) was positioned at the guiding-catheter tip, and after intracoronary flushing with saline, pressure equalization was performed. The pressure wire was advanced into the target vessel for pressure recordings. The image of the position of the pressure wire was taken in the supine position. Resting mean aortic pressure (Pa) and mean distal intracoronary pressure (Pd) were recorded, and during hyperemia by intravenous administration of 180
Intracoronary pressure measurements. FFR was measured in the supine position. Subsequently, patients were turned to a prone position. To ensure that the pressure wire’s sensor is located in the same sites, side branches or tortuous parts were used as landmarks; then, FFR was similarly measured. FFR, fractional flow reserve.
Metoprolol 20 mg was administered orally 2 hours before CT scan, and landiolol 0.125 mg/kg was additionally administered intravenously if necessary, targeting a heart rate <70 beats/min. All patients took nitroglycerin spray 0.3 mg just before the CT scan. Coronary CT was performed using a CT scanner with 80 detector rows (Aquilion PRIME SP, CANON Medical Systems Corporation, Tochigi, Japan). All scans were taken in the supine position with the patients holding their breaths at full inspiration. The following acquisition parameters were used: slice thickness 0.5 mm, tube voltage 120 kV, variable tube current 300–600 mA, rotation time 0.35 seconds, and pitch 0.175. All images were electronically retrieved on a workstation (SYNAPSE VINCENT FN-7941 Version 4.6.0003, FUJIFILM, Tokyo, Japan) and analyzed using an application (Coronary Analysis Version 4.6, FUJIFILM, Tokyo, Japan). The Pa site was positioned at the ostium of each coronary artery on the CT image, and using side branches or tortuous parts as a landmark, the Pd site was decided on the CT image. Two CT images matching the heights from the CT table were aligned, and height differences between Pa and Pd were measured (Figure
Height differences between Pa and Pd measurement by heart CT. Pa site was positioned at the ostium of the coronary artery on the CT image, and using side branches or tortuous parts as a landmark, Pd site was decided on the CT image. Two CT images matching the heights from the CT table were aligned, and the height differences between Pa and Pd were measured. CT, coronary tomography; Pa, mean aortic pressure; Pd, mean distal intracoronary pressure.
A theoretical correction for resting Pd/Pa and FFR values was performed by adding physically expectable hydrostatic pressure of 0.077 mmHg per mm height difference to the distal coronary pressure wire sensor site (Pd), calculating the ratio of specific gravity of mercury (13.55 g/cm3) and blood (1.05 g/cm3) [
Continuous variables were presented as means with standard deviation and categorical variables as numbers and percentages. Resting Pd/Pa and FFR values were compared between the two positions using a paired
Results were considered statistically significant at a
Overall, 23 patients with 27 lesions were prospectively enrolled during the study period. Patient characteristics are summarized in Table
Patient characteristics.
| |
---|---|
Age (years) | 64.8 ± 9.3 |
Male | 19 (83%) |
Hypertension | 14 (61%) |
Diabetes mellitus | 8 (35%) |
Dyslipidemia | 12 (52%) |
Smoking | 5 (22%) |
Family history | 2 (9%) |
Chronic kidney disease | 4 (17%) |
Hemodialysis | 0 (0%) |
Congestive heart failure | 1 (4%) |
Old myocardial infarction | 10 (43%) |
Previous PCI | 8 (35%) |
Previous CABG | 2 (9%) |
EF (%) | 62.1 ± 12.3 |
Peripheral artery disease | 0 (0%) |
Old cerebral infarction | 1 (4%) |
COPD | 0 (0%) |
|
|
Number of disease vessels | |
0 | 1 (4%) |
1 | 10 (43%) |
2 | 12 (52%) |
3 | 0 (0%) |
|
|
Medication | |
Antiplatelet agent | 14 (61%) |
Anticoagulation | 2 (9%) |
Beta-blocker | 6 (26%) |
Renin-angiotensin system inhibitors | 10 (43%) |
Statin | 14 (61%) |
Calcium channel blocker | 6 (26%) |
Oral diabetes drugs | 3 (13%) |
Insulin | 1 (4%) |
Data are expressed as mean ± SD and numbers (%). COPD, chronic obstructive pulmonary disease; EF, ejection fraction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft.
Lesion characteristics.
| |
---|---|
Diagnosis | |
Stable angina | 14 (52%) |
Silent myocardial ischemia | 11 (41%) |
Old myocardial infarction | 2 (7%) |
|
|
Lesion | |
LAD | 11 (41%) |
LCX | 10 (37%) |
RCA | 6 (22%) |
|
|
Type | |
A/B1 | 21 (78%) |
B2/C | 6 (22%) |
Data are expressed as numbers (%). LAD, left anterior descending artery; LCX, left circumflex artery: RCA, right coronary artery.
LAD takes an upward course, whereas LCX takes a downward course in the supine position. RCA initially takes an upward course, runs horizontally, and then takes a downward course. Figure
Anatomical position of LAD, LCX, and RCA. LAD takes an upward course, whereas LCX takes a downward course. RCA initially takes an upward course, runs horizontally, and then takes a downward course. LAD distal (Pd) is higher than the LMT ostium (Pa). LCX distal (Pd) is lower than the LMT ostium (Pa). RCA distal (Pd) is lower than the RCA ostium (Pa). LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; LMT, left main trunk.
Height and pressure differences between distal pressure sensor and catheter tip.
Height differences (Pa–Pd) (mm) | (mmHg) | |
---|---|---|
LAD ( |
−47.8 ± 14.6 | 3.7 ± 1.1 |
LCX ( |
+23.5 ± 8.5 | 1.8 ± 0.7 |
RCA ( |
+29.2 ± 9.4 | 2.3 ± 0.7 |
Data are expressed as mean ± SD. In the position where Pd is higher than Pa, it is represented by a minus sign, whereas in the position where Pd is lower than Pa, it is represented by a plus sign. LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; Pa, mean aortic; Pd, mean distal intracoronary pressure.
In LAD, resting Pd/Pa was significantly higher in the prone position than in the supine position (0.97 ± 0.05 vs 0.89 ± 0.04;
Resting Pd/Pa and FFR values in the supine and prone positions. Resting Pd/Pa and FFR values in the supine and prone positions in LAD (a, b), LCX (c, d), and RCA (e, f). Data are expressed as mean ± SD. LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; SD, standard deviation; FFR, fractional flow reserve.
Resting Pd/Pa and FFR values corrected by hydrostatic pressure in both positions were nearly equal (0.93 ± 0.04 vs 0.93 ± 0.05 and 0.76 ± 0.08 vs 0.77 ± 0.08, in LAD (Figures
Resting Pd/Pa and FFR values corrected by hydrostatic pressure in the supine and prone positions. Resting Pd/Pa and FFR values corrected by hydrostatic pressure in the supine and prone positions in LAD (a, b), LCX (c, d), and RCA (e, f). Data are expressed as mean ± SD. LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; SD, standard deviation; FFR, fractional flow reserve.
Comparison of FFR values corrected by hydrostatic pressure in the supine and prone positions. These plots show the linear regression analysis of FFR values corrected by hydrostatic pressure in the supine and prone positions in LAD (a), LCX (b), and RCA (c). LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; FFR, fractional flow reserve.
Compared with differences in FFR values between the supine and prone positions, those of the corrected FFR values were significantly lower in LAD, LCX, and RCA (0.08 ± 0.03 vs 0.01 ± 0.01,
The present study demonstrated that hydrostatic pressure variations due to height levels in Pa and Pd influence intracoronary pressure measurements and affect resting Pd/Pa and FFR values, by using measurements in the supine and prone positions in vivo. Our results revealed significantly lower values of resting Pd/Pa and FFR in the LAD supplying anterior coronary territories in the supine positions, whereas LCX or RCA with posterior coronary territories had significantly higher resting Pd/Pa and FFR values. Resting Pd/Pa and FFR values corrected by hydrostatic pressure in both positions were almost equal in LAD, LCX, and RCA.
The influence of hydrostatic pressure on the results of intracoronary pressure measurements was recently demonstrated in vitro [
During extraction of the pressure wires in the healthy LAD in the supine positions, FFR values were often showed to gradually increase. In FFR measurement of LCX or RCA, resting Pd/Pa may reach >1.00 in some cases. These two phenomena may be explained by hydrostatic pressure. Given that the mean height differences were larger in LAD than in LCX or RCA, it was speculated that the influence of hydrostatic pressure between the supine and prone positions was larger in LAD than in LCX or RCA. In fact, the mean bias of FFR, caused by hydrostatic pressure, was −0.046, +0.026, and +0.030 in LAD, LCX, and RCA, respectively, in this study. The mean pressure differences calculated from height differences in LAD were 3.7 mmHg in our populations. When Pa is 100 mmHg, Pd is increased by 3.7 mmHg for adjustment and corrected FFR is increased by 0.037. If Pa is 50 mmHg, corrected FFR is increased by 0.074, which is twice the value of 0.037. The lower the blood pressure, the greater the influence on FFR value.
It was reported that from the analysis of coronary artery anatomy with 70 CTs, LAD takes an upward course, whereas LCX takes a downward course in all patients, RCA initially takes an upward course and then takes a downward course to the posterolateral branch (RPL), and the right posterior descending artery (RPD) takes an upward course again in the direction of the LV apex [
Although several reports have demonstrated that noninvasive FFR derived from CT and invasive FFR had a good correlation, these have not been compared in LAD, LCX, and RCA [
The cutoff FFR values such as those reported in FAME [
According to the pivotal study, FFR is the relation of the difference between coronary pressure distal to a stenosis (Pd) and mean central venous pressure (Pv) and the difference between mean aortic pressure (Pa) and Pv [FFR = (Pd − Pv)/(Pa − Pv)] [
This study has several limitations. First, the number of cases was small; thus, the measured differences did not deny the abundant data reported so far in many studies on FFR. Second, the height differences were measured using cardiac CT, which is not perfectly accurate. Third, when turning the patient to the prone position, the height difference may not be opposite to that in the supine position. Fourth, it is unclear whether a particular group of patients (those with obesity and emphysema) can influence the differences shown between the supine and prone positions. Fifth, as the catheter and pressure wire were reinserted, the distal sensor site may be different between both positions. Given that we had to pay attention to both positions of the pressure wire and catheter tip, which can be removed easily while inserting and conversely entering deep into the coronary artery during withdrawal, it may be difficult to achieve precisely similar measurement positions. Sixth, in our study, we used a standard value of 1.05 as the mass density of blood. Seventh, as FFR was measured using a 4-Fr catheter, measurements might be inaccurate compared with that when using 5-Fr or larger catheters.
Our results revealed significantly lower values of resting Pd/Pa and FFR in LAD supplying the anterior coronary territories in the supine positions, whereas LCX or RCA with posterior coronary territories had significantly higher resting Pd/Pa and FFR values. Cutoff FFR values may need to be separately examined by LAD, LCX, and RCA or be examined using FFR values corrected by hydrostatic pressure in future studies.
The data used to support the findings of this study are included within the supplementary information file.
The authors declare that they have no conflicts of interest.
The supplementary material file contains the data of patient characteristics, lesion characteristics, and height differences between distal pressure sensor and catheter tip on CT. COPD, chronic obstructive pulmonary disease; EF, ejection fraction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft LAD, left anterior descending artery; LCX, left circumflex artery: RCA, right coronary artery; AP, angina pectoris; OMI, old myocardial infarction; SMI, silent myocardial ischemia.