Distal Coronary Pressure Research Articles

Comparison of Nitroglycerin-Induced Pressure Ratio Drop and Resting Full-Cycle Ratio in a Pressure Wire Study

Background/Objectives: The acute drop in distal coronary pressure (Pd)-to-aortic pressure (Pa) ratio after intracoronary nitroglycerin (NTG-Pd/Pa) administration is an acceptable estimate of fractional flow reserve (FFR). We aimed to compare the diagnostic performance of NTG-Pd/Pa with that of the resting full-cycle ratio (RFR) in predicting the binary results of FFR. Methods: This study included two prospective studies registered under the numbers NCT04700397 and NCT03693157. Altogether, 202 vessels were included. The optimal cutoff of NTG-Pd/Pa for predicting FFR ≤ 0.8 was identified and validated in another prospective registry. We used the McNemar’s test and the DeLong method to compare the diagnostic efficiency of NTG-Pd/Pa vs. RFR in predicting FFR ≤ 0.8 in a pooled cohort. Results: NTG-Pd/Pa was strongly correlated with FFR (r = 0.945, p < 0.001). The NTG-Pd/Pa cutoff for predicting FFR ≤ 0.8 was 0.85 in both the derivation and validation cohorts. The area under the receiver-operating characteristic curve (AUC) and accuracy in predicting FFR ≤ 0.8 were higher for NTG-Pd/Pa than for RFR in the pooled cohort (AUC 0.97 vs. 0.91, p < 0.001; accuracy 91% vs. 84%, p < 0.001). The sensitivity and negative predictive values were also higher for NTG-Pd/Pa than for RFR (all p < 0.05). The specificity and positive predictive value were numerically higher for NTG-Pd/Pa than for RFR (all p > 0.05). Conclusions: The diagnostic performance of NTG-Pd/Pa may surpass that of the RFR in predicting the binary results of the FFR.

Invasive quantitative assessment of coronary microvascular dysfunction in patients with hypertrophic cardiomyopathy

Abstract Background Patients (P) with hypertrophic cardiomyopathy (HCM) commonly suffer from coronary microvascular dysfunction (CMD) - the affection of function/structure of the coronary microvasculature. Invasive assessment of CMD through thermodilution methods allows for the calculation of coronary flow reserve (CFR) and index of microvascular resistance (IMR). These methods, while extensively studied in the context of non-obstructive coronary artery disease and myocardial infarction, have not been thoroughly validated in HCM P. Objectives To invasively assess the presence of CMD in P with HCM and to determine clinical predictors of invasively assessed CMD. Methods In a prospective single-centre study, we opportunistically recruited consecutive adult P with an established diagnosis of HCM with or without LVOTO that had an indication to pursue elective coronarography – such as pre-procedural evaluation for alcoholic septal ablation (ASA) or exclusion of epicardial coronary artery disease. P characteristics and coronary hemodynamic invasive assessment data were extracted. CFR was calculated as the ratio between resting and hyperemia mean transit times (TmnRest;TmnHyper). IMR was calculated as the ratio between distal coronary pressure (Pd) and the inverse of TmnHyper (IMR=Pd/TmnHyper-1). A cutoff of ≤22.0 in IMR, an ≥d 2 in CFR was used. We excluded P with end-stage HCM (LV EF <50% and/or or left ventricular wall thinning), or with epicardial coronary artery disease. Continuous variables were reported as mean ± SD or median and IQR depending on data distribution pattern and categorical data as frequencies and percentages. A linear regression model was used to test predictors of IMR and CFR involvement. Results 25 HCM P with a mean age of 63±10 years were included, 14 (56%) were female. In 20 (80%) of the P the cause for coronary angiography was ASA. All P referred for ASA had LVOTO and were on beta-blocker therapy (Table 1.). Median CFR was 2.5 [1.5-3] and median IMR was 19 [14-22], both within normal range. A total of 13 (44%) P had a reduced CFR and 5 (20%) of P had an increased IMR. 14 P (56%) had an altered CFR or IMR value, with the presence of a functional CMD phenotype in 10 P (40%) (Table 2). Angina was associated with a higher IMR (5.3, 95% CI - 0.05-10, p=0.053) and for each +1 increase in CCS a larger increase in the likelihood of a higher IMR was observed (CCS 1, +7 (95%CI 0.68 – 14); CCS 2, +9 (95%CI 4 – 14); CCS 3, 10 (95%CI 2 – 18)). A similar but non significant trend was observed for higher CCS correlating with lower CFR (Table 3). Conclusion In a prospective cohort of HCM P submited to invasive angiographic evaluation 56% had at least one invasive measure compatible with CMD. Angina, and a higher degree of anginal symptoms correlated positively with the presence of higher IMR and therefore with a higher level of CMD. In the future, we intend to correlate these findings with multimodality imaging/clinical outcomes.Patient characteristics and LR results

The impact of hydrostatic pressure on fractional flow reserve in saphenous vein grafts

Abstract Background Intracoronary physiological measurements can be subject to the influence of hydrostatic pressure. Saphenous vein grafts (SVGs) diverge in origin and trajectory from native coronary arteries, which may increase the susceptibility of fractional flow reserve (FFR) measurements to be impacted by the hydrostatic pressures. The precise impact of SVG anatomy on physiological pressure indices remains unknown at present. Purpose We sought to study the impact of SVG anatomy on FFR. Methods Included were symptomatic patients with prior coronary artery bypass grafting and at least one non-occluded SVG, who underwent coronary computed tomography angiography (CCTA) preceding invasive coronary angiography. SVG course and height excursion were reconstructed based on the CCTA images. Similarly to native coronary arteries, the impact of hydrostatic pressure on FFR was calculated by adding 0.077 mmHg to the distal coronary pressure for every millimeter height difference in a supine position between the SVG ostium and the position of the pressure wire tip. Results In total, 74 patients (mean age 71 ± 7 years; 85% male) with 87 SVGs were included. A total of 76 SVGs underwent interrogation by FFR. The height difference between SVG ostium and pressure wire tip position was largest for single SVGs to the circumflex artery (Cx; - 55.1 ± 17.0 mm), followed by sequential SVGs to the Cx (- 53.1 ± 17.7 mm) and to the right coronary artery (RCA; - 36.7 ± 21.6 mm). Corrected FFR was significantly lower as compared to uncorrected FFR in single SVGs to the Cx (0.85 ± 0.17 vs. 0.90 ± 0.18), and sequential SVGs to the Cx (0.92 ± 0.14 vs. 0.96 ± 0.15) and the RCA (0.82 ± 0.20 vs. 0.85 ± 0.21) (P<0.001 for all). Conclusions Hydrostatic pressure related to the course anatomy of SVGs notably affects FFR values, resulting in an overestimation of FFR in SVGs to the Cx and sequential SVGs to the RCA. In these SVGs, FFR values near the cutoff value should be interpreted cautiously.

Comparison of fully angiography-derived versus a hybrid of angiography and pressure-wire-derived approach to assess coronary microvascular resistance: the OxAMI-Hybrid study

Abstract Background Despite growing evidence of its clinical implications, assessment of coronary microvascular dysfunction (CMD) remains limited in routine clinical practice. Hence, there is an increasing interest in angiography-derived indices to encourage assessment of CMD in the cardiac catheterisation laboratory. We investigate here a novel approach, IMRhybrid, using a combination of pressure-wire-based assessment of distal coronary pressure (Pd) and an angiography-derived surrogate of coronary flow. Methods Patients were enrolled to the OxAMI-Hybrid study. The accuracy of IMRhybrid was assessed in diagnosing CMD using fully pressure wire and bolus thermodilution Index of Microcirculatory Resistance (IMR) as a reference. The accuracy of IMRhybrid was then compared against a fully angiography-derived index of microvascular resistance (IMRangio). Based on previous work, angiography-derived IMR, IMRangio, was calculated as IMRangio = Quantitative Flow Ratio (QFR) ado x Pahyperaemia x TIMI Frame Count (TFC) hyperaemia / Frame Rate. Conversely, IMRhybrid was expressed as IMRhybrid = Pdhyperaemia x TFChyperaemia / Frame Rate, where frame rate was fixed at 15 frame per second for both indices. In both cases, TFC/frame rate represented angiography-derived mean transit time, mTt in hyperaemia. Results 60 patients were enrolled prospectively, of which 28 with acute coronary syndrome and 32 with stable coronary artery disease. A total of 66 vessel analyses were performed. Both IMRhybrid and IMRangio correlated with IMR (rho=0.51, p <0.001 and rho=0.51, p <0.001 respectively) and showed good and comparable overall diagnostic accuracy in predicting IMR ≥ 25 (83.3% and 75.4% respectively) with a receiver operator curve (ROC) analyses showing an AUC of 0.82 and 0.81 respectively (p for comparison= 0.97). Conclusion Both approaches, IMRhybrid and IMRangio provide viable and comparable methods of assessing CMD which correlate with bolus thermodilution-based IMR, retaining good diagnostic accuracy. IMRhybrid is a simple alternative to conventional bolus thermodilution-based IMR, offering the advantage of being suitable with any pressure wire system.A: IMR, B: QFR, C: TFCA+C: IMRhybrid, B+D: IMRangio

The interplay between coronary microvascular resistance, arterial reservoir function and coronary flow reserve: unravelling the significance of high microvascular resistance

Abstract Background Beyond the observation that patients with low CFR indicating presence of coronary microvascular dysfunction (CMD) have an unfavourable prognosis compared to patients with preserved CFR, recent large multicentre trials [1-2] have shown that increased minimal hyperaemic microvascular resistance (HMR or IMR) ,neither on top of the low CFR nor alone, does not play a role as a prognostic factor for ischemia in nonobstructive coronary artery disease (INOCA) patients. Purpose This study investigates the pathophysiological interactive processes in CMD and no-CMD groups with high and low HMR taking into account potential adaptive mechanisms that alter arterial reservoir function [3] associated with microvascular resistance and systemic vasomotor response in INOCA patients. Methods Analysis was conducted on 312 unique unobstructed vessels (FFR>0.80) from 258 patients (73% male) enrolled in the DEFINE-FLOW [4] study. CFR and HMR were quantified using intracoronary Doppler and pressure measurements. Vessels were categorized into four groups based on high and low CFR and HMR using the best available cut-off values (2.5 for both). Arterial reservoir capacity (ARC) and related parameters [3] were quantified using reservoir-excess pressure (Preservoir and Pexcess) analysis of averaged aortic and distal coronary pressure waveforms in CMD (CFR<2.5) and no-CMD (CFR≥2.5) subgroups. (Figure 1-2) Results Compared to vessels without CMD, functional and structural CMD have increased Pexcess (p:0.007) and a rapid decline in diastolic pressure (DRCcoronary p<0.001, DRCaortic, p<0.05), indicating the ongoing systemic hemodynamic superfluous state despite locally suppressed resting blood flow in the structural CMD. Higher baseline microvascular resistance (BMR) was associated with increased reservoir pressure (r:0.302, p<0.001). The vessels with preserved CFR despite high HMR are characterised by uniquely increased ARC (p:0.014), effectively diminished Pexcess (p:0.010), which parallels the local (highest BMR p<0.001) and global (lowest DRCaortic, p<0.05) vasomotor response, that normalizes the systemic and local hyperperfusion, and ultimately regains an adequate flow reserve (CFR) (p<0.001). The high HMR in this group was mainly due to increased resting tonus unlike structural CMD, evident by the highest RRR (BMR/HMR).(p<0.001) (Figure 1-2) Conclusion(s) The high HMR despite preserved CFR vessels form a unique-adaptive group, characterised by substantially increased arterial reservoir capacity and effectively diminished Pexcess, by means of an adaptive vasomotor response which manifests locally in the coronary bed as pronouncedly augmented BMR & RRR, and globally as reduced DRC in the aortic pressure waveform. This adaptive myogenic response normalising resting flow and ongoing systemic and local hyperperfusion ultimately regains an adequate flow reserve (CFR).Figure 1.Methods and Main FindingsFigure 2.Visual Abstract

Correlation and consistency between resting full-cycle ratio and fractional flow reserve in assessing coronary artery function in a Chinese real-world cohort with non-ST-segment elevation acute coronary syndrome: a retrospective observational study

ObjectiveThe study aimed to investigate the correlation and consistency between resting full-cycle ratio (RFR) and fractional flow reserve (FFR) in functional assessment of coronary arteries in a Chinese real-world cohort...

Pd/Pa fluctuation with continuous ATP administration indicates inaccurate FFR measurement caused by insufficient hyperemia.

Continuous intravenous adenosine triphosphate (ATP) administration is the standard method for inducing maximal hyperemia in fractional flow reserve (FFR) measurements. Several cases have demonstrated fluctuations in the ratio of mean distal coronary pressure to mean arterial pressure (Pd/Pa) value during ATP infusion, which raised our suspicions of FFR value inaccuracy. This study aimed to investigate our hypothesis that Pd/Pa fluctuations may indicate inaccurate FFR measurements caused by insufficient hyperemia. We examined 57 consecutive patients with angiographically intermediate coronary lesions who underwent fractional flow reverse (FFR) measurements in our hospital between November 2016 and September 2018. Pd/Pa was measured after continuous ATP administration (150μg/kg/min) via a peripheral forearm vein for 5min (FFRA); and we analyzed the FFR value variation in the final 20s of the 5min, defining 'Fluctuation' as variation range > 0.03. Then, 2mg of nicorandil was administered into the coronary artery during continued ATP infusion, and the Pd/Pa was remeasured (FFRA+N). Fluctuations were observed in 23 of 57 patients. The cases demonstrating discrepancies of > 0.05 between FFRA and FFRA+N were observed more frequently in the fluctuation group than in the non-fluctuation group (12/23 vs. 1/34; p < 0.0001). The discrepancy between FFRA and FFRA+N values was smaller in the non-fluctuation group (mean difference ± SD; -0.00026 ± 0.04636 vs. 0.02608 ± 0.1316). Pd/Pa fluctuation with continuous ATP administration could indicate inaccurate FFR measurements caused by incomplete hyperemia. Additional vasodilator administration may achieve further hyperemia when Pd/Pa fluctuations are observed.

Diagnostic performance of pressure-bounded coronary flow reserve.

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79%, sensitivity of 83%, specificity of 78%, positive predictive value of 48%, negative predictive value of 95%. The discordance presenting CFRthermo < 2.0 and pb-CFR ≥ 2.0 was associated with diffuse disease (P < 0.001). The discordance presenting CFRthermo ≥ 2 and pb-CFR < 2 was associated with a high FFR (P = 0.002). Pb-CFR showed moderate correlation and poor agreement with CFRthermo. Pb-CFR might be reliable in excluding epicardial coronary artery disease and microcirculatory disorders.

Coronary microvascular resistance comparison of coronary arteries with and without considering vascular diameter: A retrospective, single-center study.

Measurement of coronary microvascular resistance (MR) is essential for diagnosing nonocclusive coronary artery ischemia, but whether coronary branches of different diameters can be similarly assessed using hyperemic microvascular resistance index (hMVRI) calculated from average peak velocity (APV) remains unclear. We investigated the relationship between coronary arteries of different diameters and hMVRI. Thirty patients with suspected angina pectoris and nonobstructive coronary stenosis with fractional flow reserve >0.8 underwent evaluation of all coronary arteries using a Doppler velocity and pressure-equipped guidewire. Quantitative coronary angiography (QCA) was used to analyze vessel diameter (DQCA). Coronary blood flow (CBFQCA) was calculated as πDQCA 2/4 (0.5 × APV) and hMVRIQCA as distal coronary pressure divided by CBFQCA during maximal hyperemia. The hMVRI was significantly higher for the right coronary artery than for the left anterior descending artery, but no significant differences between arteries were seen for CBFQCA and hMVRIQCA. Although the correlation between CBFQCA and APV was weak, CBFQCA divided into three groups according to DQCA showed very strong correlations with APV. Slopes of the straight line between APV and CBFQCA for small-, middle-, and large-diameter groups were 0.48, 0.30, and 0.21, respectively, with slope decreasing as diameter increased. Comparative evaluation of MR in coronary branches with varying vessel diameters requires vessel diameter to be accounted for.

Angiography-based coronary microvascular assessment with and without intracoronary pressure measurements: a systematic review.

In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography. The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations. We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%. Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography. Central illustration. Comparative assessment of image-based methods quantifying microvascular resistance with and without intracoronary pressure measurements. Angiography-based methods rely on angiography alone to calculate the microvascular resistance by utilizing angiographic frame counting to extrapolate coronary flow (Q) and subsequently deriving distal coronary pressure using fluid dynamic equations. Combined angiography- and pressure-based methods utilize invasive intracoronary pressure gradients measured during rest and maximal vasodilation to determine coronary flow in their calculation of microvascular resistance. The combined methods showed more acceptable levels of agreement with their reference methods compared to angiography-based methods alone.

Impact of height difference between coronary ostium and location of intracoronary pressure sensor on fractional flow reserve measurements

Abstract Background Fractional flow reserve (FFR) is the most verified index to date in invasively evaluating lesion-specific myocardial ischemia. During FFR measurements, distal coronary pressure (Pd) can be influenced by hydrostatic pressure change resulted from the height difference (HD) between coronary ostium and location of distal pressure sensor. We aimed to investigate the impact of aorto-coronary HD on FFR measurement in each coronary artery. Methods We retrospectively analyzed 257 patients who underwent FFR measurement and coronary computed tomography angiography (CCTA) within a year. HD was measured by CCTA as the vertical distance between coronary ostium and a matched point of distal coronary pressure sensor identified on coronary angiography. Results The location of Pd sensor was higher in left anterior descending artery (LAD) (-4.47±1.33cm), whereas lower in left circumflex artery (LCX) (2.54±1.05cm) and right coronary artery (RCA) (2.05±1.25cm) than the coronary ostium. Compared with the original FFR values, corrected FFR by HD was higher in LAD (0.79±0.09, 0.82±0.09, P&amp;lt;0.05) and tended to be lower in LCX and RCA (0.87±0.07, 0.85±0.08, p=0.21; 0.87±0.10, 0.86±0.10, p=0.49, respectively). Based on FFR cut-off value of 0.8, the concordance rate between the FFR and corrected FFR was 77.8%, 92.5%, and 100% in LAD, LCX, and RCA, respectively. Conclusion During FFR measurements, HD between coronary ostium and distal pressure sensor may affect interpretation of disease severity and FFR-guided treatment decision of coronary artery disease.

The integration of angio-IMR, QFR and FFR for the detection of ischemia

Abstract Background Fractional flow reserve (FFR) and quantitative flow ratio (QFR) are important tools to assess coronary-specific ischemia, but ischemia may be obscured in the presence of coronary microvascular dysfunction (CMD). Wire free angiography based index of microcirculatory resistance (angio-IMR) might aid in identifying ischemic territories with normal FFR or QFR. Purpose First we sought to validate angio-IMR against invasive resistance indices and [15O]H2O positron emission tomography (PET) derived resistance. Secondly, we investigated whether angio-IMR can help identifying ischemic vessels with normal FFR/QFR. Methods In this PACIFIC 1 and 2 sub study symptomatic patients underwent [15O]H2O PET and invasive coronary angiography with routine three vessel FFR. Invasive hyperemic microvascular resistance (HMR) and IMR were measured in a sub set of patients. A FFR/QFR ≤0.80 and hyperemic myocardial blood flow (hMBF) ≤2.3 ml/min/g were considered ischemic. Microvascular resistance on PET was defined as the ratio of mean distal coronary pressure to MBF. Angio-IMR, QFR and PET analyses were performed by core labs blinded to invasive angiography results. Results Among 259 patients (mean age 61 ± 9 years, 188 (73%) male) 494 vessels were included. Invasive IMR and or HMR were measured in 95 vessels. Angio-IMR did not correlate with invasive HMR/IMR for the right coronary artery (RCA) but correlated weakly with invasive HMR (r=0.39, p=0.03) and moderately (r=0.48, p&amp;lt;0.01) with invasive IMR for the left coronary artery (LCA). The RCA was excluded for further analysis. A very weak correlation between angio-IMR and PET resistance was observed (r=0.17, p&amp;lt;0.01). Territories with ischemia and a normal FFR showed a higher angio-IMR than ischemic territories with reduced FFR (31.3 ± 13.8 vs 22.2 ± 10.3, p&amp;lt;0.01). The same was observed after stratification by QFR/PET results (34.3 ± 15.5 vs 23.9 ± 9.9, p&amp;lt;0.01). Results remained consistent after stratification for diameter stenosis percentage. Conclusions A weak to moderate correlation was found between angio-IMR and invasive resistance indices for the LCA. In territories with an ischemic perfusion angio-IMR was higher in those with a normal FFR/QFR compared to patients with a reduced FFR/QFR. Integration of FFR/QFR and angio-IMR might lead to superior vessel-specific ischemia detection.

The importance of baseline fractional flow reserve to detect significant coronary artery stenosis in different patient populations.

Fractional flow reserve (FFR) assessment compares the blood flow on either side of a blockage in the coronary artery and indicates how severe the stenosis is in the artery. Intravenous adenosine is widely used to achieve conditions of stable hyperaemia for the measurement of FR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Therefore, FFR has some limitations, such as the side effects of adenosine and the long procedure time. In addition, there are not enough studies on the evaluation of the baseline ratio of distal coronary pressure to aortic pressure (Pd/Pa) according to standard cut-off values in coronary stenosis under special clinical conditions. This study aimed to assess the diagnostic power of the baseline FFR value for critical coronary stenosis and to determine its predictive value in special patient groups. This retrospective study included 158 patients, who were stratified as Q1 (< 0.89), Q2 (0.89-0.92), Q3 (0.93-0.95) and Q4 (> 0.95) based on baseline FFR values. The baseline Pd/Pa value, the change in adenosine FFR and the raw FFR change were recorded. Its predictive value was also calculated for specific patient groups. The threshold value of baseline FFR level for predicting critical stenosis was ≤ 0.92 with a sensitivity of 92.8% and a specificity of 82% (upper limit of Q2 cartilage). Patients with a baseline FFR value ≤ 0.92 had a 58.4-fold greater likelihood of a critical outcome compared with patients with a baseline FFR value > 0.92 (OR: 58.4; 95% CI: 20.3-124.6). In patients with a baseline FFR ≤ 0.92, the Q1 group had a 10.23-fold higher odds of critical stenosis compared with the Q2 group (OR: 10.23; 95% CI: 2.14-48.84). The same values had similar diagnostic power for all specific patient groups. The baseline FFR value could be used to predict critical coronary stenosis in our patients and had similar value for predicting lesion severity in all the subgroups.

Coronary microcirculatory dysfunction can be assessed by positive dicrotic wave and amplitude index on resting distal coronary pressure waveform, a newly developed index.

Some lesions have high resting distal coronary pressure/aortic pressure (Pd/Pa) despite low fractional flow reserve (FFR). This study aimed to assess microcirculatory dysfunction as a possible basal mechanism. Patients were grouped into two according to coffee intake (caffeine 222 mg) before coronary angiography. Through an adenosine-induced Pd/Pa decrease, amplitude index was calculated by dividing the difference between the highest pressure after the inflection point and the minimal diastolic pressure by the pulse pressure on the Pd waveform. In 130 coronary lesions (caffeine group, n = 69; non-caffeine group, n = 61) from 113 patients, the amplitude index through the adenosine-induced Pd/Pa decrease in all lesions was 0.54 ± 0.11 at resting Pd/Pa and 0.44 ± 0.12 at FFR (P < 0.0001). The positive dicrotic wave distribution on a maximal hyperaemia (FFRnicr)-resting Pd/Pa graph was analysed. In lesions with FFRnicr <0.80 on the FFRnicr-resting Pd/Pa graph, the resting Pd/Pa was divided into three zones based on Pd/Pa values: high-remaining, intermediate, and low. The high-remaining zone had a higher amplitude index than the intermediate zone (0.60 ± 0.09 vs. 0.48 ± 0.12; P < 0.005); the low zone lesions had no inflection point (no amplitude index). The high-remaining zone correlated with a larger positive dicrotic wave than the intermediate zone (94 vs. 30%; P < 0.005). Most lesions in the high-remaining zone corresponded to the caffeine group. In severe coronary stenosis, a high-remaining resting Pd/Pa with a high amplitude index or a positive dicrotic wave on the resting Pd waveform suggests microcirculatory dysfunction, such as insufficient arteriolar dilation reactive to myocardial ischaemia. UMIN000046883.

Randomized, crossover, controlled trial on the modulation of cardiac coronary sinus hemodynamics to develop a new treatment for microvascular disease: Protocol of the MACCUS trial.

Microvascular angina (MVA) is a frequent condition for which our understanding of the disease pathophysiology and therapeutic perspectives remain unsatisfactory. The current study is designed to test whether an improvement in microvascular resistances could be achieved by elevating backward pressure in the coronary venous system, based on the hypothesis that an increase in hydrostatic pressure could cause a dilatation of the myocardial arterioles, resulting in a reduction of vascular resistances. This approach might have potential clinical implications, as it might suggest that interventions aimed at increasing coronary sinus (CS) pressure might result in a decrease in angina in this subset of patients. The aim of our single-center, sham-controlled, crossover randomized trial is to investigate the effect of an acute increase in CS pressure on a number of parameters of coronary physiology, including parameters of coronary microvascular resistance and conductance. A total of 20 consecutive patients with angina pectoris and coronary microvascular dysfunction (CMD) will be enrolled in the study. Hemodynamic parameters including aortic and distal coronary pressure, CS and right atrial pressure, and the coronary microvascular resistance index will be measured at rest and during hyperemia in a randomized crossover design during incomplete balloon occlusion ("balloon") and with the deflated balloon in the right atrium ("sham"). The primary end point of the study is the change in index of microvascular resistances (IMR) after acute modulation of CS pressure, while key secondary end points include changes in the other parameters. The aim of the study is to investigate whether occlusion of the CS is associated with a decrease in IMR. The results will provide mechanistic evidence for the development of a treatment for patients with MVA. https://clinicaltrials.gov/, identifier NCT05034224.

Validation of pressure-bounded coronary flow reserve using invasive coronary physiologic assessment.

Coronary flow reserve (CFR) represents entire coronary compensatory capacity. While CFR assessment is recommended to identify patients at an increased risk of cardiovascular events and coronary microvascular dysfunction, invasive CFR measurement is often technically challenging. Although not well validated yet, pressure-bounded CFR (pbCFR) has been proposed as a simple surrogate to estimate impaired CFR. In this study, we evaluated coronary physiological characteristics of low pbCFR using detailed invasive assessment. Invasive physiological assessment including resting ratio of distal coronary pressure to aortic pressure (Pd/Pa), fractional flow reserve (FFR), resting and hyperemic mean transit time, index of microcirculatory resistance (IMR), CFR, resistive reserve ratio, and microvascular resistance reserve (MRR) was performed in 107 patients in the left anterior descending coronary artery. pbCFR was calculated only with resting Pd/Pa and FFR. Patients were divided into low pbCFR and non-low pbCFR groups. Of 107 patients, 50 (46.7%) had low pbCFR. FFR (0.90 ± 0.05 vs. 0.83 ± 0.05, p < 0.001), hyperemic mean transit time (0.27 ± 0.17 vs. 0.21 ± 0.12, p = 0.04), and IMR (20.4 ± 13.2 vs. 15.0 ± 9.1, p = 0.01) were significantly higher in the low pbCFR group than their counterpart. While directly measured CFR did not differ significantly (4.4 ± 2.3 vs. 5.1 ± 2.8, p = 0.18), MRR was lower in the low pbCFR group (5.4 ± 3.0 vs. 6.8 ± 3.8, p = 0.047). The rates of CFR < 2.0 and IMR ≥ 25 were not significantly different between the 2 groups. In conclusion, although CFR did not differ significantly, IMR and MRR were impaired in patients with low pbCFR, suggesting pbCFR as a potential surrogate of coronary microvascular function in clinical practice.

Changes in coronary collateral function after successful chronic total occlusion percutaneous coronary intervention.

Contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) incorporates wire escalation and dissection/re-entry recanalisation strategies. The purpose of the study was to investigate changes in collateral function after CTO PCI and to identify whether the mode of successful recanalisation influences collateral function regression. Patients scheduled for elective CTO PCI with evidence of viability in the CTO territory by noninvasive imaging were included in this study. After successful CTO PCI, the aortic pressure (Pa) and distal coronary artery wedge pressure (Pw) during balloon occlusion were measured, both in a resting state and during infusion of intravenous adenosine, allowing the calculation of the pressure-derived collateral pressure index at rest and hyperaemia (CPIrest and the collateral fractional flow reserve [FFRcoll], respectively). Measurements were repeated 3 months later during angiographic follow-up. Eighty-one patients had physiological measurements at baseline and follow-up. In the final cohort the mean age was 64 years and 82% were male. The mean maximal stent diameter and total stent length were 3.2±0.5 mm and 68±31 mm, respectively. Successful strategies were antegrade wiring (64.2%), antegrade dissection re-entry (8.6%), and retrograde dissection re-entry (27.1%). Between the index procedure and follow-up, wedge pressure decreased from 34±11 mmHg to 21±8.5 mmHg (p<0.01), respectively. FFRcoll changed from 0.34±0.11 to 0.19±0.09 (p<0.01) at follow-up and CPIrest from 0.40±0.14 to 0.17±0.09 (p<0.01). Absolute maximum collateral flow decreased from 55±32 ml/min directly after PCI to 38±24 ml/min (p<0.01). There was no relation between the recanalisation technique and changes in FFRcoll. There was a significant reduction in collateral flow over time, independent of the recanalisation technique.

Abstract 15187: Comparison of Resting and Hyperemic Coronary Physiological Indices to Evaluate Myocardial Bridging in Patients With Angina and No Obstructive Coronary Arteries

Introduction: A hemodynamically significant myocardial bridge (MB) is an important diagnosis in patients with angina and no obstructive coronary arteries (ANOCA). The most appropriate intracoronary functional assessment to distinguish an incidental vs. hemodynamically significant MB remains unclear. We compared the ability of several resting and hyperemic physiological indices to identify a hemodynamically significant MB. Methods: We prospectively studied 11 patients with ANOCA and an MB confirmed by intravascular ultrasound (IVUS). All patients had intracoronary functional testing at rest, including instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), and the ratio of distal coronary pressure (Pd)/aortic pressure (Pa). These measurements were repeated at hyperemia, including adenosine fractional flow reserve (FFR), dobutamine diastolic FFR (dFFR), iFR, and RFR. Resting iFR and RFR ≤ 0.89; resting Pd/Pa ≤ 0.91; hyperemic FFR, iFR, and RFR ≤ 0.8; and dFFR ≤ 0.76 were considered indicative of hemodynamic significance of an MB. Dobutamine dFFR was considered as reference standard. Results: At rest, iFR and RFR were significant in 6 and 7 patients respectively, while Pd/Pa was significant in 6. Adenosine FFR was significant in only 4 patients. With dobutamine, iFR and RFR were significant in 8 and 9 patients, respectively, and dFFR was significant in 9. Resting Pd/Pa and hyperemic iFR had a strong positive Spearman's rank correlation coefficient with dFFR (Figure). By kappa statistics, dobutamine iFR and RFR had almost perfect agreement with dobutamine dFFR. Conclusion: In patients with ANOCA who have an MB by IVUS, intracoronary physiology assessment is necessary to determine if the MB is hemodynamic significant. While adenosine FFR is an insufficient measure, diastolic indices such as dobutamine dFFR, iFR, or RFR may identify hemodynamic significance, although whether one diastolic index outperforms another requires further evaluation.

Pressure- and 3D-derived coronary flow reserve with hydro-static pressure correction: a validation by intracoronary Doppler measurements

Abstract Purpose To develop a method of coronary flow reserve (CFR) calculation derived from three-dimensional (3D) coronary angiographic parameters and intracoronary pressure data during fractional flow reserve (FFR) measurement. Methods Altogether 19 coronary arteries of 16 native and 3 stented vessels were reconstructed in 3D. The measured distal intracoronary pressures were corrected to the hydrostatic pressure based on the height differences between the levels of the vessel orifice and the sensor position. Classical fluid dynamic equations were applied to calculate the flow during the resting state and vasodilatation on the basis of morphological data and intracoronary pressure values. 3D-derived coronary flow reserve (CFRp-3D) was defined as the ratio between the calculated hyperemic and the resting flow and was compared to the CFR values simultaneously measured by the Doppler sensor (CFRDoppler). Results Haemodynamic calculations using the distal coronary pressures corrected for hydrostatic pressures showed a strong correlation between the individual CFRp-3D values and the CFRDoppler measurements (r=0.89, p&amp;lt;0.0001). Hydrostatic pressure correction increased the specificity of the method from 46.1% to 92.3% for predicting an abnormal CFRDoppler &amp;lt;2. Conclusions CFRp-3D calculation with hydrostatic pressure correction during FFR measurement facilitates a comprehensive haemodynamic assessment, supporting the complex evaluation of macro- and microvascular coronary artery disease. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Debrecen

Relation of hyperemic response during fractional flow reserve measurement to coronary flow reserve

BackgroundCoronary flow reserve (CFR) represents entire coronary compensatory capacity, while fractional flow reserve (FFR) is a standard to evaluate functional severity of epicardial coronary artery disease (CAD). ΔFFR, a decrease in a ratio of mean distal coronary pressure to aortic pressure (Pd/Pa) at rest to FFR, is conceptually associated with coronary microvascular function. This study aimed to evaluate the relation of ΔFFR to CFR in patients with stable CAD. MethodsWe performed resting Pd/Pa and FFR measurements in a total of 309 vessels with intermediate coronary artery stenosis in 242 patients. ΔFFR was defined as (resting Pd/Pa – FFR), and pressure bounded-CFR was calculated to estimate low CFR. Vessels were divided as the low CFR and non-low CFR groups. ResultsOf 309 vessels, low CFR was observed in 101 (32.7 %). While FFR values were similar (0.78 ± 0.11 vs. 0.78 ± 0.09, p = 0.84), resting Pd/Pa (0.85 ± 0.08 vs. 0.93 ± 0.04, p < 0.001) and ΔFFR (0.07 ± 0.06 vs. 0.15 ± 0.06, p < 0.001) were significantly lower in the low CFR group than in the non-low CFR group. The receiver operating characteristic curve analysis indicated that ΔFFR was predictive for low CFR (area under the curve 0.84, best cut-off value 0.08, p < 0.001). Multivariable analysis identified lower ΔFFR, the left anterior descending coronary artery, and lower hemoglobin and higher brain natriuretic peptide levels as factors associated with low CFR. ConclusionsIn patients with stable CAD, lower ΔFFR was significantly associated with low CFR in intermediate coronary stenosis in patients with stable CAD. ΔFFR may be a simple, practical, and useful surrogate to identify patients with impaired CFR.