Impact of core laboratory assessment on treatment decisions and clinical outcomes using combined fractional flow reserve and coronary flow reserve measurements - DEFINE-FLOW core laboratory sub-study.

Objective: 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.

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.

Computed Tomography-Mediated Registration of Trapeziometacarpal Articular Cartilage Using Intraarticular Optical Coherence Tomography and Cryomicrotome Imaging: A Cadaver Study.

Objective: Accurate, high-resolution imaging of articular cartilage thickness is an important clinical challenge in patients with osteoarthritis, especially in small joints. In this study, computed tomography (CT) mediated catheter-based optical coherence tomography (OCT) was utilized to create a digital reconstruction of the articular surface of the trapeziometacarpal (TMC) joint and to assess cartilage thickness in comparison to cryomicrotome data.

Design: Using needle-based introduction of the OCT probe, the articular surface of the TMC joint of 5 cadaver wrists was scanned in different probe positions with matching CT scans to record the intraarticular probe trajectory.

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.

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

Unlabelled: 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.

Optimization of Vascular Casting for Three-Dimensional Fluorescence Cryo-Imaging of Collateral Vessels in the Ischemic Rat Hindlimb.

Development of collateral vessels, arteriogenesis, may protect against tissue ischemia, however, quantitative data on this process remain scarce. We have developed a technique for replicating the entire arterial network of ischemic rat hindlimbs in three dimensions (3D) based on vascular casting and automated sequential cryo-imaging. Various dilutions of Batson's No.

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 (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.

Transmural distribution and connectivity of coronary collaterals within the human heart.

Despite the importance of collateral vessels in human hearts, a detailed analysis of their distribution within the coronary vasculature based on three-dimensional vascular reconstructions is lacking. This study aimed to classify the transmural distribution and connectivity of coronary collaterals in human hearts. One normotrophic human heart and one hypertrophied human heart with fibrosis in the inferior wall from a previous infarction were obtained.

Basal stenosis resistance index derived from simultaneous pressure and flow velocity measurements.

Aims: Vasodilator-free basal stenosis resistance (BSR) equals fractional flow reserve (FFR) accuracy for ischaemia-inducing stenoses. Nonetheless, basal haemodynamic variability may impair BSR accuracy compared with hyperaemic stenosis resistance (HSR). We evaluated the influence of basal haemodynamic variability, as encountered in practice, on BSR accuracy versus HSR when derived from simultaneous pressure and flow velocity measurements, and determined its diagnostic performance for HSR-defined significant stenoses.

Selective subepicardial localization of monocyte subsets in response to progressive coronary artery constriction.

Following myocardial infarction and atherosclerotic lesion development, monocytes contribute to myocardial protection and repair, while also partaking in myocardial ischemic injury. The balance of proinflammatory and reparative monocyte subsets is crucial in governing these therapeutic and pathological outcomes. Myocardial ischemic damage displays heterogeneity across the myocardium, whereby the subendocardium shows greatest vulnerability to ischemic damage.

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

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.

Fundamentals in clinical coronary physiology: why coronary flow is more important than coronary pressure.

Wide attention for the appropriateness of coronary stenting in stable ischaemic heart disease (IHD) has increased interest in coronary physiology to guide decision making. For many, coronary physiology equals the measurement of coronary pressure to calculate the fractional flow reserve (FFR). While accumulating evidence supports the contention that FFR-guided revascularization is superior to revascularization based on coronary angiography, it is frequently overlooked that FFR is a coronary pressure-derived estimate of coronary flow impairment.

Microsphere skimming in the porcine coronary arteries: Implications for flow quantification.

Particle skimming is a phenomenon where particles suspended in fluid flowing through vessels distribute disproportionately to bulk fluid volume at junctions. Microspheres are considered a gold standard of intra-organ perfusion measurements and are used widely in studies of flow distribution and quantification. It has previously been hypothesised that skimming at arterial junctions is responsible for a systematic over-estimation of myocardial perfusion from microspheres at the subendocardium.

A quantitative high resolution voxel-wise assessment of myocardial blood flow from contrast-enhanced first-pass magnetic resonance perfusion imaging: microsphere validation in a magnetic resonance compatible free beating explanted pig heart model.

Aims: To assess the feasibility of high-resolution quantitative cardiovascular magnetic resonance (CMR) voxel-wise perfusion imaging using clinical 1.5 and 3 T sequences and to validate it using fluorescently labelled microspheres in combination with a state of the art imaging cryomicrotome in a novel, isolated blood-perfused MR-compatible free beating pig heart model without respiratory motion.

Methods And Results: MR perfusion imaging was performed in pig hearts at 1.

Detection and quantification methods of monocyte homing in coronary vasculature with an imaging cryomicrotome.

Cellular imaging modalities are important for revealing the behavior and role of monocytes in response to neovascularization progression in coronary artery disease. In this study we aimed to develop methods for high-resolution three-dimensional (3D) imaging and quantification of monocytes relative to the entire coronary artery network using a novel episcopic imaging modality. In a series of ex vivo experiments, human umbilical vein endothelial cells and CD14+ monocytes were labeled with fluorescent live cell tracker probes and infused into the coronary artery network of excised rat hearts by a Langendorff perfusion method.

Head-to-head comparison of basal stenosis resistance index, instantaneous wave-free ratio, and fractional flow reserve: diagnostic accuracy for stenosis-specific myocardial ischaemia.

Aims: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index.

Methods And Results: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC).

Physiological basis and long-term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity.

Background: Discordance between fractional flow reserve (FFR) and coronary flow velocity reserve (CFVR) may reflect important coronary pathophysiology but usually remains unnoticed in clinical practice. We evaluated the physiological basis and clinical outcome associated with FFR/CFVR discordance.

Methods And Results: We studied 157 intermediate coronary stenoses in 157 patients, evaluated by FFR and CFVR between April 1997 and September 2006 in which revascularization was deferred.

Increased hyperaemic coronary microvascular resistance adds to the presence of myocardial ischaemia.

Aims: It has been argued that hyperaemic microvascular resistance (HMR), defined as the ratio of mean distal coronary pressure to flow velocity, is overestimated in the presence of a coronary stenosis compared to actual microvascular resistance (MR), due to neglecting collateral flow. We aimed to test the hypothesis that HMR allows accurate identification of microvascular functional abnormalities by evaluating the association between high or low HMR and the presence of myocardial ischaemia on non-invasive stress testing.

Methods And Results: Myocardial perfusion scintigraphy was performed in 228 patients, with 299 lesions to identify reversible myocardial ischaemia.

Impact of hyperaemic microvascular resistance on fractional flow reserve measurements in patients with stable coronary artery disease: insights from combined stenosis and microvascular resistance assessment.

Background: Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease.

Methods And Results: We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR.

Wave speed in human coronary arteries is not influenced by microvascular vasodilation: implications for wave intensity analysis.

Wave intensity analysis and wave separation are powerful tools for interrogating coronary, myocardial and microvascular physiology. Wave speed is integral to these calculations and is usually estimated by the single-point technique (SPc), a feasible but as yet unvalidated approach in coronary vessels. We aimed to directly measure wave speed in human coronary arteries and assess the impact of adenosine and nitrate administration.

Innate collateral segments are predominantly present in the subendocardium without preferential connectivity within the left ventricular wall.

Functional collateral vessels often stem from outward remodelling of pre-existing connections between perfusion territories. Knowledge of the distribution and morphology of innate collateral connections may help in identifying myocardial areas with protection against risk for ischaemia. The coronary network of six healthy canine hearts was investigated with an imaging cryomicrotome.

Functional coronary stenosis severity assessed from the mean pressure gradient-velocity relationship obtained by contrast medium-induced submaximal hyperaemia.

Aims: First, to establish the diagnostic performance of the pressure gradient at a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis pressure gradient-velocity (dP-v) relationship obtained by administration of adenosine and, second, to determine whether dPv can be assessed from contrast medium-induced submaximal hyperaemia.

Methods And Results: Distal coronary pressure and velocity were simultaneously recorded in 64 patients during the response to intracoronary injection of adenosine. dPv was assessed at velocities between 20 and 50 cm/s.

Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study.

Objectives: This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study.

Background: FFR is an index of the severity of coronary stenosis that has been clinically validated in 3 prospective randomized trials. iFR and Pd/Pa are nonhyperemic pressure-derived indices of the severity of stenosis with discordant reports regarding their accuracy with respect to FFR.

Myocardial perfusion distribution and coronary arterial pressure and flow signals: clinical relevance in relation to multiscale modeling, a review.

Coronary artery disease, CAD, is associated with both narrowing of the epicardial coronary arteries and microvascular disease, thereby limiting coronary flow and myocardial perfusion. CAD accounts for almost 2 million deaths within the European Union on an annual basis. In this paper, we review the physiological and pathophysiological processes underlying clinical decision making in coronary disease as well as the models for interpretation of the underlying physiological mechanisms.