Coronary stenosis physiology appraisal: Handle with care

Ischemic heart disease (IHD) may occur due to the presence of a coronary artery stenosis and microvascular dysfunction. In patients with coronary artery stenosis, the diagnostic goal is to assess the functional stenosis severity, i.e. the potential of the stenosis to limit myocardial perfusion, in order to select appropriate treatment. Invasive diagnostic tests provide this opportunity. These tests can be performed at resting myocardial blood flow (baseline) and during induced vasodilation of the coronary microcirculation (hyperemia). Indices derived from intracoronary measurements have been increasingly adopted in the last decade. However, the oversimplification of coronary pathophysiology underlying the derivation of these diagnostic tools may affect the choice for treatment and their prognostic power at the individual patient level. This thesis sought to provide further insights into the invasive physiological assessment of coronary artery stenosis severity, by means of combined intracoronary pressure and velocity measurements. In particular, the effect of changes in myocardial oxygen demand, coronary hemodynamics variability and procedural aspects on current baseline and hyperemic functional indices were investigated throughout this thesis

Hemodynamic effects of epicardial stenoses.

This chapter starts by a brief review of coronary physiology in terms of pressure-flow relationships and effects of vessel distensibility on microvascular resistance to lay the foundation for interpretation of coronary stenosis hemodynamics. The fluid dynamics of stenosis pressure gradient, resistance, and its dependency on flow and stenosis dimensions is outlined in the next section. Special consideration is given to serial lesions, stenosis compliance, and diffuse coronary narrowing. The last section discusses the hemodynamic effect of coronary epicardial stenoses on coronary blood flow and the need for integration of multiple physiological parameters to arrive at a well-founded procedural decision for an individual patient suffering from ischemic heart disease

Usefulness of Proximal Coronary Wave Speed for Wave Intensity Analysis in Diseased Coronary Vessels

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

Temporal dissociation between the minimal distal-to-aortic pressure ratio and peak hyperemia during intravenous adenosine infusion

The present study sought to compare the temporal relation between maximal coronary flow (peak hyperemia) and minimal coronary-to-aortic pressure ratio (Pd/Pa) for intracoronary (IC) and intravenous (IV) adenosine administration. Peak hyperemia is assumed to coincide with the minimal Pd/Pa 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 Pd/Pa for different stenosis severities and varying Pa 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 Pd/Pa reached a minimum (0.82 ± 0.01) 22 ± 7 s later (P < 0.05), when Pa had declined by 6.1% and hyperemic velocity by 4.5% (P < 0.01). Model outcomes corroborated the role of variable Pa in this dissociation. In contrast, maximal flow and minimal Pd/Pa coincided for IC adenosine, with IV-equivalent peak velocities and a higher Pd/Pa ratio (0.86 ± 0.01, P < 0.01). Hemodynamic variability during continuous IV adenosine infusion can lead to temporal dissociation of minimal Pd/Pa and peak hyperemia, in contrast to IC adenosine injection, where maximal velocity and minimal Pd/Pa 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.NEW & NOTEWORTHY 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(2+) antagonist

Discordance between pressure drift after wire pullback and intracoronary distal pressure offset affects stenosis physiology appraisal

Background: 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. Methods: 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. Results: 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. Conclusions: 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

Influence of increased heart rate and aortic pressure on resting indices of functional coronary stenosis severity

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 9 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-makin

Transcatheter Replacement of Stenotic Aortic Valve Normalizes Cardiac-Coronary Interaction by Restoration of Systolic Coronary Flow Dynamics as Assessed by Wave Intensity Analysis

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). 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 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. 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 wave

Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect—combined pressure and Doppler FLOW velocity measurements (DEFINE-FLOW) trial: Rationale and trial design

Background: 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. Aim: 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. Methods: 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 ( 0.80 and CFR ≥ 2.0. Enrollment has been completed, and final follow-up will occur in November 2019