Abstract
Aims
Atherosclerotic plaque development has been associated with wall shear stress (WSS). However, the multidirectionality of blood flow, and thus of WSS, is rarely taken into account. The ...purpose of this study was to comprehensively compare five metrics that describe (multidirectional) WSS behaviour and assess how WSS multidirectionality affects coronary plaque initiation and progression.
Methods and results
Adult familial hypercholesterolaemic pigs (n = 10) that were fed a high-fat diet, underwent imaging of the three main coronary arteries at three-time points 3 (T1), 9 (T2), and 10–12 (T3) months. Three-dimensional geometry of the arterial lumen, in combination with local flow velocity measurements, was used to calculate WSS at T1 and T2. For analysis, arteries were divided into 3 mm/45° sectors (n = 3648). Changes in wall thickness and final plaque composition were assessed with near-infrared spectroscopy–intravascular ultrasound, optical coherence tomography imaging, and histology. Both in pigs with advanced and mild disease, the highest plaque progression rate was exclusively found at low time-averaged WSS (TAWSS) or high multidirectional WSS regions at both T1 and T2. However, the eventually largest plaque growth was located in regions with initial low TAWSS or high multidirectional WSS that, over time, became exposed to high TAWSS or low multidirectional WSS at T2. Besides plaque size, also the presence of vulnerable plaque components at the last time point was related to low and multidirectional WSS. Almost all WSS metrics had good predictive values for the development of plaque (47–50%) and advanced fibrous cap atheroma (FCA) development (59–61%).
Conclusion
This study demonstrates that low and multidirectional WSS promote both initiation and progression of coronary atherosclerotic plaques. The high-predictive values of the multidirectional WSS metrics for FCA development indicate their potential as an additional clinical marker for the vulnerable disease.
Graphical Abstract
Graphical Abstract
BACKGROUND—Aortic valve stenosis (AS) can cause angina despite unobstructed coronary arteries, which may be related to increased compression of the intramural microcirculation, especially at the ...subendocardium. We assessed coronary wave intensity and phasic flow velocity patterns to unravel changes in cardiac–coronary interaction because of transcatheter aortic valve implantation (TAVI).
METHODS AND RESULTS—Intracoronary pressure and flow velocity were measured at rest and maximal hyperemia in undiseased vessels in 15 patients with AS before and after TAVI and in 12 control patients. Coronary flow reserve, systolic and diastolic velocity time integrals, and the energies of forward (aorta-originating) and backward (microcirculatory-originating) coronary waves were determined. Coronary flow reserve was 2.8±0.2 (mean±SEM) in control and 1.8±0.1 in AS (P<0.005) and was not restored by TAVI. Compared with control, the resting backward expansion wave was 45% higher in AS. The peak of the systolic forward compression wave was delayed in AS, consistent with a delayed peak aortic pressure, which was partially restored after TAVI. The energy of forward waves doubled after TAVI, whereas the backward expansion wave increased by >30%. The increase in forward compression wave with TAVI was related to an increase in systolic velocity time integral. AS or TAVI did not alter diastolic velocity time integral.
CONCLUSIONS—Reduced coronary forward wave energy and systolic velocity time integral imply a compromised systolic flow velocity with AS that is restored after TAVI, suggesting an acute relief of excess compression in systole that likely benefits subendocardial perfusion. Vasodilation is observed to be a major determinant of backward waves.
Background:
Wave speed is needed to separate net wave intensity into forward and backward traveling components. However, wave speed in diseased coronary arteries cannot be assessed from hemodynamic ...measurements obtained distal to a stenosis. Wave speed inherently depends on arterial wall properties which should be similar proximal and distal to a stenosis. Our hypothesis is that proximal wave speed can be used to separate net wave intensity obtained distal to a stenosis.
Methods:
We assessed coronary wave speed using the sum-of-squares single-point technique (SPc) based on simultaneous intracoronary pressure and flow velocity measurements in human coronary arteries. SPc at resting flow was determined in diseased coronary vessels of 12 patients both proximal and distal to the stenosis. In seven of these vessels, distal measurements were additionally obtained after revascularization by stent placement. SPc was also assessed at two axial locations in 14 reference vessels without a stenosis.
Results:
(
1
) No difference in SPc was present between proximal and distal locations in the reference vessels. (
2
) In diseased vessels with a focal stenosis, SPc at the distal location was paradoxically larger than SPc proximal to the stenosis (28.4 ± 3.7 m/s vs. 18.3 ± 1.8 m/s,
p
< 0.02), despite the lower distending pressure downstream of the stenosis. The corresponding separated wave energy tended to be underestimated when derived from SPc at the distal compared with the proximal location. (
3
) After successful revascularization, SPc at the distal location no longer differed from SPc at the proximal location prior to revascularization (21.9 ± 2.0 m/s vs. 20.8 ± 1.9 m/s,
p
= 0.48). Accordingly, no significant difference in separated wave energy was observed for forward or backward waves.
Conclusion:
In diseased coronary vessels, SPc assessed from distal hemodynamic signals is erroneously elevated. Our findings suggest that proximal wave speed can be used to separate wave intensity profiles obtained downstream of a stenosis. This approach may extend the application of wave intensity analysis to diseased coronary vessels.
The quadratic stenosis pressure gradient-velocity (ΔP-v) relationship can be derived from combined pressure and flow velocity measurements during the response to a hyperemic stimulus. Since pressure ...gradient must be zero at no flow, the zero-flow intercept of this curve reveals peri-procedural drift. ...for 17% of the tracings, unacceptable drift during the physiological appraisal was not noticeable at the ostium.
Abstract only
Aim
To investigate the effect of intracoronary (IC) and intravenous (IV) adenosine administration on variability in coronary and stenosis hemodynamics.
Methods
In 12 diseased coronary ...vessels (25‐56% DS), aortic pressure (Pa), distal pressure (Pd) and flow velocity (v) were simultaneously measured at baseline and hyperemia induced by IC (40 μg bolus) and IV adenosine administration (140 μg/kg/min). At baseline and throughout the hyperemic response we obtained cycle‐averaged pressure and velocity signals to derive microvascular resistance (MR = Pd/v) and FFR= Pd/Pa. From fitted stenosis pressure gradient‐velocity (ΔP‐v) relations, we determined ΔP at v= 30 cm/s (dPv30).
Results
Maximal v was similar for IC and IV adenosine (50 ± 4 vs. 54 ± 5 cm/s) with no difference in MR (1.73 ± 0.10 vs. 1.74 ± 0.13 mmHg/cm/s). However, MR during IV hyperemia rose between 9 and 135% in the post‐peak period, with concomitant fluctuations in v (13 to 61% decline) and pressures (up to 34% decline). Minimal FFR coincided with peak v for IC adenosine, but occurred 21 ± 8 s after peak v for IV adenosine, when Pa had decreased by 13% and HR increased by 25% vs. baseline. IV and IC derived stenosis ΔP‐v relations followed a stable common quadratic relationship, with no difference in dPv30.
Conclusion
IV adenosine caused persistent systemic and coronary hemodynamic variability. IC adenosine yielded comparable hyperemia with minor effects on systemic hemodynamics. Consistent ΔP‐v relations and dPv30 provide reliable means for stenosis evaluation free from maximal vasodilation.
Drift is a well-known issue affecting intracoronary pressure measurements. A small pressure offset at the end of the procedure is generally considered acceptable, while repeat assessment is advised ...for drift exceeding ±2 mmHg. This practice implies that drift assessed after wire pullback equals that at the time of stenosis appraisal, but this assumption has not been systematically investigated. Our aim was to compare intra-and post-procedural pressure sensor drift and assess benefits of correction for intra-procedural drift and its effect on diagnostic classification.
In 70 patients we compared intra- and post-procedural pressure drift for 120 hemodynamic tracings obtained at baseline and throughout the hyperemic response to intracoronary adenosine. Intra-procedural drift was derived from the intercept of the stenosis pressure gradient-velocity relationship. Diagnostic reclassification after correction for intra-procedural drift was assessed for the mean distal-to-aortic pressure ratio at baseline (Pd/Pa) and hyperemia (fractional flow reserve, FFR), and corresponding stenosis resistances.
Post- and intra-procedural drift exceeding the tolerated threshold was observed in 73% and 64% of the hemodynamic tracings, respectively. Discordance in terms of acceptable drift level was present for 42% of the tracings, with avoidable repeat physiological assessment in 25% and unacceptable intra-procedural drift unrecognized at final drift check in 17% of the tracings. Correction for intra-procedural drift caused higher reclassification rates for baseline than hyperemic functional indices.
Post-procedural pressure drift frequently does not match drift during physiological assessment. Tracing-specific correction for intra-procedural drift can potentially lower the risk of inadvertent diagnostic misclassification and prevent unnecessary repeats.
Display omitted
•Measuring intracoronary pressure and flow velocity allows tracing-specific drift assessment•Pressure drift checked at the end of the procedure frequently does not match drift during physiological appraisal•Tracing-specific drift correction has potential to lower risk of diagnostic misclassification and avoid unnecessary repeats
It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow ...reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases. Optimal management of these discordant cases requires further study.
The aim of the study was to determine the prognostic value of combined FFR and CFR measurements to predict the 24-month rate of major adverse cardiac events. Secondary end points include repeatability of FFR and CFR, angina burden, and the percentage of successful FFR/CFR measurements which will not be excluded by the core laboratory.
This prospective, nonblinded, nonrandomized, and multicenter study enrolled 455 subjects from 12 sites in Europe and Japan. Patients underwent physiologic lesion assessment using the 0.014” Philips Volcano ComboWire XT that provides simultaneous pressure and Doppler velocity sensors. Intermediate coronary lesions received only medical treatment unless both FFR (≤0.8) and CFR (<2.0) were below thresholds. The primary outcome is a 24-month composite of death from any cause, myocardial infarction, and revascularization.
The DEFINE-FLOW study will determine the prognostic value of invasive CFR assessment when measured simultaneously with FFR, with a special emphasis on discordant classifications. Our hypothesis is that lesions with an intact CFR ≥ 2.0 but reduced FFR ≤ 0.8 will have a 2-year outcome with medical treatment similar to lesions with FFR> 0.80 and CFR ≥ 2.0. Enrollment has been completed, and final follow-up will occur in November 2019.
The role of combined FFR/CFR measurements in decision-making on coronary revascularization remains unclear. DEFINE-FLOW prospectively assessed the relationship of FFR/CFR agreement with 2-year major ...adverse cardiac event (MACE) and target vessel failure (TVF) rates, and uniquely included core-laboratory analysis of all pressure and flow tracings. We aimed to document the impact of core-laboratory analysis on lesion classification, and the relationship between core-laboratory fractional flow reserve (FFR) and coronary flow reserve (CFR) values with clinical outcomes and angina burden during follow-up.
In 398 vessels (348 patients) considered for intervention, ≥1 coronary pressure/flow tracing was approved by the core-laboratory. Revascularization was performed only when both FFR(≤0.80) and CFR(<2.0) were abnormal, all others were treated medically.
MACE was lowest for concordant normal FFR/CFR, but was not significantly different compared with either discordant group (low FFR/normal CFR: HR:1.63; 95%CI:0.61–4.40; P = 0.33; normal FFR/low CFR: HR:1.81; 95%CI:0.66–4.98; P = 0.25). Moreover, MACE did not differ between discordant groups treated medically and the concordant abnormal group undergoing revascularization (normal FFR/low CFR: HR:0.63; 95%CI:0.23–1.73;P = 0.37; normal FFR/low CFR: HR:0.70; 95%CI:0.22–2.21;P = 0.54). Similar findings applied to TVF.
Patients with concordantly normal FFR/CFR have very low 2-year MACE and TVF rates. Throughout follow-up, there were no differences in event rates between patients in whom revascularization was deferred due to preserved CFR despite reduced FFR, and those in whom PCI was performed due to concordantly low FFR and CFR. These findings question the need for routine revascularization in vessels showing low FFR but preserved CFR.
Clinical trial registration: http://ClinicalTrials.govNCT02328820
•Patients with both normal fractional flow reserve and coronary flow reserve have very low 2-year rates of adverse events.•Event rates are equivalent between patients in whom revascularization was deferred due to preserved coronary flow reserve despite reduced fractional flow reserve, and those in whom revascularization was performed•Event rates are equivalent between patients in whom revascularization was deferred due to preserved fractional flow reserve despite reduced coronary flow reserve, and those in whom revascularization was performed.•These findings question the need for routine revascularization in vessels showing discordance between fractional flow reserve and coronary flow reserve
Baseline assessment of functional stenosis severity has been proposed as a practical alternative to hyperemic indices. However, intact autoregulation mechanisms may affect intracoronary hemodynamics. ...The aim of this study was to investigate the effect of changes in aortic pressure (Pa) and heart rate (HR) on baseline coronary hemodynamics and functional stenosis assessment. In 15 patients (55 ± 3% diameter stenosis) Pa, intracoronary pressure (Pd) and flow velocity were obtained at control, and during atrial pacing at 120 bpm, increased Pa (+30 mmHg) with intravenous phenylephrine (PE), and elevated Pa while pacing at sinus heart rate (PE + sHR). We derived rate pressure product (RPP = systolic Pa × HR), baseline microvascular resistance (BMR = Pd/velocity), and stenosis resistance BSR = (Pa − Pd)/velocity as well as whole-cycle Pd/Pa. Tachycardia (120 ± 1 bpm) raised RPP by 74% vs. control. Accordingly, BMR decreased by 27% (
p
< 0.01) and velocity increased by 36% (
p
< 0.05), while Pd/Pa decreased by 0.05 ± 0.02 (
p
< 0.05) and BSR remained similar to control. Raising Pa to 121 ± 3 mmHg (PE) with concomitant reflex bradycardia increased BMR by 26% (
p
< 0.001) at essentially unchanged RPP and velocity. Consequently, BSR and Pd/Pa were only marginally affected. During PE + sHR, velocity increased by 21% (
p
< 0.01) attributable to a 46% higher RPP (
p
< 0.001). However, BMR, BSR, and Pd/Pa remained statistically unaffected. Nonetheless, the interventions tended to increase functional stenosis severity, causing Pd/Pa and BSR of borderline lesions to cross the diagnostic threshold. In conclusion, coronary microvascular adaptation to physiological conditions affecting metabolic demand at rest influences intracoronary hemodynamics, which may lead to altered basal stenosis indices used for clinical decision-making.
The present study sought to compare the temporal relation between maximal coronary flow (peak hyperemia) and minimal coronary-to-aortic pressure ratio (P
/P
) for intracoronary (IC) and intravenous ...(IV) adenosine administration. Peak hyperemia is assumed to coincide with the minimal P
/P
value. However, this has not been confirmed for systemic hemodynamic variations during IV adenosine infusion. Hemodynamic responses to IV and IC adenosine administration were obtained in 12 patients (14 lesions) using combined IC pressure and flow velocity measurements. A fluid dynamic model was used to predict the change in P
/P
for different stenosis severities and varying P
Hemodynamic variability during IV adenosine hyperemia was greater than during IC adenosine, as assessed by the coefficient of variation. During IV adenosine, flow velocity peaked 28 ± 4 (SE) s after the onset of hyperemia, while P
/P
reached a minimum (0.82 ± 0.01) 22 ± 7 s later (
< 0.05), when P
had declined by 6.1% and hyperemic velocity by 4.5% (
< 0.01). Model outcomes corroborated the role of variable P
in this dissociation. In contrast, maximal flow and minimal P
/P
coincided for IC adenosine, with IV-equivalent peak velocities and a higher P
/P
ratio (0.86 ± 0.01,
< 0.01). Hemodynamic variability during continuous IV adenosine infusion can lead to temporal dissociation of minimal P
/P
and peak hyperemia, in contrast to IC adenosine injection, where maximal velocity and minimal P
/P
coincide. Despite this variability, stenosis hemodynamics remained stable with both ways of adenosine administration. Our findings suggest advantages of IC over IV adenosine to identify maximal hyperemia from pressure-only measurements.
Systemic hemodynamic variability during intravenous adenosine infusion produces substantial temporal dissociation between peak hyperemia appraised by coronary flow velocity and the minimal distal-to-aortic pressure ratio commonly used to determine functional stenosis severity. This dissociation was absent for intracoronary adenosine administration and tended to be mitigated in patients receiving Ca
antagonists.
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