Computational assessment of hemodynamics in asymmetric-type lesion of idealized coronary stenoses

Background Coronary pressure-derived fractional flow reserve (FFR) measurements are recommended for hemodynamic coronary stenosis assessment. Given temporary paralysis of the coronary microcirculation during hyperemia, pressure is, in theory, directly related to coronary flow. Pressure drop during hyperemia across a coronary stenosis, thus, provides an estimate of its restrictive effect on flow. FFR during reactive hyperemia induced by a proximal, 1-minute coronary artery balloon occlusion has been shown non-inferior to FFR as obtained by adenosine-induced hyperemia. Intracoronary ECG (icECG) is more sensitive in detecting myocardial ischemia than the surface ECG, and can be easily obtained. Purpose The present study evaluated a novel diagnostic approach based on icECG ST-segment shift remission time for hemodynamic stenosis severity assessment. Methods This was a retrospective observational trial in patients with chronic coronary syndrome, who underwent hemodynamic measurements during a brief coronary occlusion with simultaneous icECG recording during coronary angiography. The icECG recording was used for a beat-to-beat analysis of the ST-segment elevation performed by a previously developed fully autonomous algorithm. The time after release of the 1-minute ostial coronary balloon occlusion when the ST elevation reached 50% of the pre-occlusion (baseline) isoelectric line, i.e., icECG remission half time (τ-icECG; τ=tau), was obtained by the algorithm (Figure1). τ-icECG was evaluated using the simultaneously obtained FFR at a threshold of 0.80 as reference parameter. Results 139 icECGs from 119 patients were analysed, 23 had to be excluded in advance, due to incomplete icECG recording or algorithm failure. A ROC-analysis of τ at a threshold of >8s found it significantly accurate for detecting a hemodynamically relevant coronary stenosis at FFR≤0.80 (area under the ROC-curve 0.618, 95% CI 0.507-0.735, sensitivity 60%, specificity 67%, p=0.037) (Figure2). Conclusion Τ-icECG, a measure of icECG ST-elevation remission time to isoelectricity as obtained during reactive hyperemia FFR accurately detects hemodynamically relevant coronary artery stenoses at a threshold of ≥ 8 seconds.

Fractional flow reserve (FFR) measurements are recommended for assessing hemodynamic coronary stenosis severity. Intracoronary ECG (icECG) is easily obtainable and highly sensitive in detecting myocardial ischemia due to its close vicinity to the myocardium. We hypothesized that the remission time of myocardial ischemia on icECG after a controlled coronary occlusion accurately detects hemodynamically relevant coronary stenosis. This retrospective, observational study included patients with chronic coronary syndrome undergoing hemodynamic coronary stenosis assessment immediately following a strictly 1-min proximal coronary artery balloon occlusion with simultaneous icECG recording. icECG was used for a beat-to-beat analysis of the ST-segment shift during reactive hyperemia immediately following balloon deflation. The time from coronary balloon deflation until the ST-segment shift reached 37% of its maximum level, i.e., icECG ST-segment shift remission time (τ-icECG in seconds), was obtained by an automatic algorithm. τ-icECG was tested against the simultaneously obtained reactive hyperemia FFR at a threshold of 0.80 as a reference parameter. From 120 patients, 139 icECGs (age, 68 ± 10 yr old) were analyzed. Receiver operating characteristic (ROC) analysis of τ-icECG for the detection of hemodynamically relevant coronary stenosis at an FFR of ≤0.80 was performed. The area under the ROC curve was equal to 0.621 (P = 0.0363) at an optimal τ-icECG threshold of 8 s (sensitivity, 61%; specificity, 67%). τ-icECG correlated inversely and linearly with FFR (P = 0.0327). This first proof-of-concept study demonstrates that τ-icECG, a measure of icECG ST segment-shift remission after a 1-min coronary artery balloon occlusion accurately detects hemodynamically relevant coronary artery stenosis according to FFR at a threshold of ≥8 s.NEW & NOTEWORTHY Invasive hemodynamic measurements are recommended by the current cardiology guidelines to guide percutaneous coronary interventions in the setting of chronic coronary syndrome. However, those pressure-derived indices demonstrate several theoretical and practical limitations. Thus, this study demonstrates the accuracy of a novel, pathophysiology-driven approach using intracoronary ECG for the identification of hemodynamically relevant coronary lesions by quantitatively assessing myocardial ischemia remission.

Background Based on coronary computed tomography angiography (cCTA), stenoses can be detected but provides anatomical assessment solely. Fractional flow reserve based on coronary CT angiography (ML-cFFR) is gaining in importance for non-invasive hemodynamic assessment of obstructive coronary artery disease (CAD), as several large trials demonstrated significantly improvements in diagnostic accuracy to cCTA. Comparably instantaneous wave free ratio (iFR) is a novel resting index for the invasive determination of haemodynamic relevant stenoses, finds consideration in the ESC guideline on myocardial revascularization and is now of equal standing with FFR as a class IA recommendation. Purpose The aim of our study was to evaluate the on-site ML-cFFR in terms of diagnostic accuracy and clinical practicability in comparison to the iFR as the current invasive gold standard to detect hemodynamically significant coronary artery stenoses. Methods In our prospective, multi-center study, patients with CAD who had a clinically indicated cCTA and subsequent invasive coronary angiography with iFR-measurement were included. To analyse the acquired cCTA dataset we used a third-generation dual-source CT with on-site prototype ML-cFFR software that is based on a machine-learning algorithm, to determine the hemodynamic relevance of coronary stenoses. Results Between July 2017 and December 2018, in 40 of 42 cases (95%), the on-site ML-cFFR calculation was successful. Finally we enrolled 40 patients (72.5% males, mean age 66.7±11.9 years) with ML-cFFR calculation based on cCTA and iFR-measurement during ICA. The mean calculation time of the ML-cFFR values was 10.6±1.9minutes. 57 vessel specific lesions were analysed, of which 15 (26%) were determined as hemodynamically relevant stenoses by iFR (iFR≤0.89) whereas ML-cFFR classified only 14 (24.5%) as hemodynamic significant coronary stenoses (ML-cFFR≤0.80). We observed that cCTA overestimated the severity of stenoses in 27 of 40 cases, which might lead to unnecessary coronary angiographies. However, ML-cFFR detected no obstructive CAD in 26 of 40 patients (65%) and this would have resulted in a reduction of initially performed pure diagnostic coronary angiography. Estimated values sensitivity, specificity, PPV and NPV were 86.7%, 97.4%, 92.9% and 95.0%. The diagnostic accuracy of ML-cFFR in terms of iFR on a per-patient and per-lesion level was 95.0% and 96.5%. The area under the curve (AUC) on a per-lesion and per-patient basis by ML-cFFR to detect lesion specific ischemia was 0.97 and 0.96. The analysis of the correlation (Pearson's product-moment) on a per-lesion level was r=0.82 (p<0.0001) between the ML-cFFR algorithm and iFR. Conclusion(s) On-site ML-cFFR correlates excellently with the novel gold standard iFR to non-invasively detect hemodynamic significant coronary stenoses in routine clinical practice. Acknowledgement/Funding Doctor S. Baumann receives research support from Siemens and Philips Volcano. All other authors declare that they have no financial disclosure.

The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. We performed adenosine (140 micrograms.kg-1.min-1 over 4 min) and dipyridamole (up to 0.84 mg.kg-1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively (P = ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P < 0.05) tighter stenosis than in the echocardiography-negative patients (adenosine, 66.6 +/- 8.3% vs 58.0 +/- 8.9%; dipyridamole, 69.2 +/- 7.1% vs 57.7 +/- 7.6%). During both tests, left ventricular end-diastolic pressure significantly increased (P < 0.05) in echocardiography-positive patients (adenosine, 9.8 +/- 2.7 mmHg to 13.5 +/- 4.1 mmHg; dipyridamole, 10.1 +/- 2.8 mmHg to 14.1 +/- 4.3 mmHg), but not in echocardiography-negative patients. In the patients who had undergone successful angioplasty (reduction to < 50% diameter stenosis), both adenosine and dipyridamole confirmed the arteriographic success of the procedure (echocardiography negative in all patients). In this group of patients, no significant change was observed in left ventricular end-diastolic pressure during adenosine or dipyridamole infusion. Intravenous infusion of either adenosine or dipyridamole was accompanied by an obvious increase in left ventricular end-diastolic pressure only in patients with induced wall motion abnormalities. Coronary vasodilation per se has no significant effect on left ventricular end-diastolic pressure when no ischaemia is induced, disproving any clinically significant 'erectile' and adverse effects of coronary vasodilation per se.

Combined coronary and perfusion cardiovascular magnetic resonance for the assessment of coronary artery stenosis.

Fractional flow reserve (FFR) and intravascular imaging respectively provide hemodynamic and anatomical assessments of angiographic intermediate stenoses. Frequency domain optical coherence tomography (FD-OCT) is a promising high-resolution imaging modality, but its clinical use in determining severity of coronary disease has yet to be determined. There, we set out to determine the role of FD-OCT to complement FFR in the evaluation of intermediate coronary artery stenoses. FD-OCT was planned in 176 consecutive interventional procedures at our institution to delineate the proper use of FD-OCT in clinical practice. The decision to use other invasive assessments was at the discretion of the operator. This report describes an early series of the 14 patients who underwent FFR of 18 target stenoses in addition to FD-OCT. FD-OCT was successfully performed without complications in all cases. Fractional flow reserve was <0.80 in four patients, with minimal lumen areas and reference vessel diameters ranging from 1.03 to 3.47 mm(2) and 2.60 to 2.94 mm by FD-OCT, respectively. FD-OCT was important to rule out plaque rupture, erosion and thrombosis and to help guide decision to defer PCI in six patients with acute coronary syndrome and FFR > 0.80. FD-OCT was also valuable to guide PCI strategy in tandem lesions with an FFR < 0.80. This initial experience with FD-OCT suggests a potential complementary role of physiological and anatomical assessment to guide decision making in complex clinical scenarios. Future investigations are warranted to validate these findings and define the role of FD-OCT in assessing intermediate lesions.

Influence of the position of the distal pressure measurement point on the Fractional Flow Reserve using in-silico simulations

To quantify differences in regional myocardial perfusion in coronary artery stenosis by the use of dual source computed tomography (DSCT) in an animal model. In 5 pigs, an 80% stenosis of the left anterior descending artery was successfully induced by partial balloon occlusion (ischemia group). Five animals served as control group. All animals underwent contrast enhanced whole heart DSCT (Definition Flash, Siemens, Germany) perfusion imaging using a prototype electrocardiogram -triggered dynamic scan mode. Imaging was performed at rest as well as under stress conditions during continuous infusion of adenosine (240 mg/kg/min). For contrast enhancement 60 mL Iopromide 300 (Ultravist 300, Bayer-Schering Pharma, Berlin, Germany) were injected at a rate of 6 mL/s. Myocardial blood flow (MBF), first pass distribution volume, and intravascular blood volume were volumetrically quantified. In the control group MBF increased significantly from 98.2 mL/100 mL/min to 134.0 mL/100 mL/min if adenosine was administered (P = 0.0153). There were no significant differences in the perfusion parameters comparing the control and ischemia group at rest. In the ischemia group MBF under stress was 74.0 +/- 21.9 mL/100 mL/min in the poststenotic myocardium and 117.4 +/- 18.6 mL/100 mL/min in the remaining normal myocardium (P = 0.0024). DSCT permits quantitative whole heart perfusion imaging. As this technique is able to show the hemodynamic effect of high grade coronary artery stenosis, it exceeds the present key limitation of cardiac computed tomography, which currently only allows a morphologic assessment of coronary artery stenosis.

The assessment of the left main coronary artery (LMCA) stenosis by angiography is not reliable, and noninvasive tests are incapable of discriminating ischemia caused by LMCA versus other stenoses. Among patients with LMCA stenosis, both fractional flow reserve and intravascular ultrasound parameters would determine the severity of stenosis and predict the event rates. This review outlines the evidence in support of their routine use for the assessment of an ambiguous LMCA stenosis.

Cardiac CTA is increasingly asserting its position as an established tool for the detection and characterization of coronary plaque and stenosis, its morphological evaluation capability, however, falling short of hemodynamic assessment. This fact is of high relevance in the process of therapeutic decision making, which explains the dominance of functional imaging techniques, such as nuclear myocardial perfusion imaging, magnetic resonance imaging, or stress echocardiography. There are four major targets of functional imaging that are particularly critical to the selection of a revascularization procedure over medical treatment strategies: (1) Assessment of myocardial perfusion defects to identify treatable coronary artery disease (CAD); (2) Identification of myocardial perfusion status as an important prognostic factor for the occurrence of future cardiovascular events; (3) Assessment of myocardial viability to guide therapy; and (4) Evaluation of the hemodynamic relevance of detected coronary artery stenosis by flow measurements. This chapter reviews the current limitations of morphological assessment of coronary stenosis by cardiac CTA, describes available techniques for functional imaging, and enumerates its major targets, which have been well implemented in current management strategies for patients with suspected or known CAD.

Background: Fractional Flow Reserve (FFR) is a method that enables the hemodynamic assessment of coronary artery stenosis. The Systemic Inflammatory Response Index (SIRI) is a new marker calculated by multiplying the neutrophil-to-lymphocyte ratio (NLR) with the monocyte count. It is indicative of the presence and severity of coronary artery disease. This study evaluates the relationship between the functional significance of FFR measurements and the SIRI in intermediate coronary stenosis. Methods: A total of 294 patients with 50-70% stenosis in their coronary arteries based on quantitative measurement following angiography who underwent FFR measurement were included in the study before the FFR procedure. Total and differential leukocyte counts and routine biochemical tests were performed. Results: A total of 37% of the patients were found to have a positive FFR, while 63% had a negative FFR. Significant differences were observed in the neutrophil count, monocyte count, Systemic Inflammation Response Index (SIRI), total cholesterol, and amount of adenosine used between the groups (p < 0.05). A SIRI value of 1.16 was 77% sensitive and 55% specific for FFR positivity. Multivariate logistic regression analysis identified the SIRI as an independent predictor of FFR positivity. Conclusions: Our study has demonstrated that high values of the SIRI may serve as a new biomarker for predicting FFR positivity.

PurposesThe objective was to evaluate the accuracy of a novel CT dynamic angiographic imaging (CT-DAI) algorithm for rapid fractional flow reserve (FFR) measurement in patients with coronary artery disease (CAD).Materials and MethodsThis retrospective study included 14 patients (age 58.5 ± 10.6 years, 11 males) with CAD who underwent stress dynamic CT myocardial perfusion scanning with a dual-source CT scanner. The included patients had analyzable proximal and distal coronary artery segments adjacent to the stenosis in the perfusion images and had corresponding invasive catheter-based FFR measurements for that stenosis. An in-house software based on the CT-DAI algorithm was used to compute FFR using the pre- and post- lesion coronary time-enhancement curves obtained from the stress myocardial perfusion images. The CT-DAI derived FFR values were then compared to the corresponding catheter-based invasive FFR values. A coronary artery stenosis was considered functionally significant for FFR value <0.8.ResultsThe CT-DAI derived FFR values were in agreement with the invasive FFR values in all 15 coronary arteries in 14 patients, resulting in 100% per-vessel and per-patient diagnostic accuracy. FFR derived using CT-DAI (M = 0.768, SD = 0.156) showed an excellent linear correlation (R = 0.910, P < .001) and statistical indifference (P= .655) with that measured using invasive catheter-based method (M = 0.796, SD = 0.149). Bland-Altman analysis showed no significant proportional bias.ConclusionThe novel CT-DAI algorithm can reliably compute FFR across a coronary artery stenosis directly from dynamic CT myocardial perfusion images, facilitating rapid on-site hemodynamic assessment of the epicardial coronary artery stenosis in patients with CAD.

The paradigm has been shifted from anatomy-guided to physiology-guided management of coronary artery disease. Hence, intense attention has been focused on whether hemodynamic assessment can be achieved by noninvasive imaging modalities. Among them, coronary computed tomography (CT) has potentials to allow the assessment of ischemia-causing coronary stenosis due to its excellent spatial resolution. Currently, myocardial perfusion imaging, CT-derived computed fractional flow reserve and transluminal attenuation gradient are promising CT-based techniques to detect myocardial ischemia. Furthermore, its application can be extended beyond the detection of ischemia and to the measurement of hemodynamic forces acting on the plaque and the simulation of treatment plans using virtual stenting technique.

ObjectivesWe sought to develop an automatic method for correcting common errors in phasic pressure tracings for physiology‐guided interventions on coronary and valvular stenosis.BackgroundEffective coronary and valvular interventions rely on accurate hemodynamic assessment. Phasic (subcycle) indexes remain intrinsic to valvular stenosis and are emerging for coronary stenosis. Errors, corrections, and clinical implications of fluid‐filled catheter phasic pressure assessments have not been assessed in the current era of ubiquitous, high‐fidelity pressure wire sensors.MethodsWe recruited patients undergoing invasive coronary physiology assessment. Phasic aortic pressure signals were recorded simultaneously using a fluid‐filled guide catheter and 0.014″ pressure wire before and after standard calibration as well as after pullback. We included additional subjects undergoing hemodynamic assessment before and after transcatheter aortic valve implantation. Using the pressure wire as reference standard, we developed an automatic algorithm to match phasic pressures.ResultsRemoving pressure offset and temporal shift produced the largest improvements in root mean square (RMS) error between catheter and pressure wire signals. However, further optimization <1 mmHg RMS error was possible by accounting for differential gain and the oscillatory behavior of the fluid‐filled guide. The impact of correction was larger for subcycle (like systole or diastole) versus whole‐cycle metrics, indicating a key role for valvular stenosis and emerging coronary pressure ratios.ConclusionsWhen calibrating phasic aortic pressure signals using a pressure wire, correction requires these parameters: offset, timing, gain, and oscillations (frequency and damping factor). Automatically eliminating common errors may improve some clinical decisions regarding physiology‐based intervention.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have emerged as the invasive diagnostic tools of choice for hemodynamic assessment of the severity of CAD (coronary artery disease). We sought to comprehensively review the evidence on the utility of hemodynamic assessment of the coronary stenoses after percutaneous coronary intervention (PCI) using FFR/iFR, mechanisms of positive post-PCI iFR/FFR, and the clinical impact of significant residual ischemia. The evidence on the utility of the post-PCI hemodynamic assessment has accumulated over the last few years. The post hoc analysis from the FAME 1 and FAME 2 data shows that higher post-PCI FFR is associated with better symptomatic improvement and lower event rate with larger increase in delta FFR (∆ FFR: post-PCI FFR - pre-PCI FFR). Unlike pre-PCI FFR, a consensus has not been established on the optimal value of post-PCI FFR, though multiple studies point toward better clinical outcomes with higher post-PCI FFR and larger ∆ FFR. Visual assessment of adequate stent apposition by coronary angiography is insufficient in evaluating for residual ischemia. The hemodynamic evaluation of residual ischemia by post-PCI FFR/iFR yields clinically relevant data and allows for appropriate post PCI optimization.