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Background: The hyperaemic stenosis resistance (HSR) index was introduced to provide a more comprehensive indicator of the haemodynamic severity of a coronary lesion. HSR combines both the pressure drop across a lesion and the flow through it. As such, HSR overcomes the limitations of the more traditional fractional flow reserve (FFR) or coronary flow reserve (CFR) indices., Aims: We aimed to identify the diagnostic and prognostic value of HSR and evaluate the clinical implications., Methods: Patients with chronic coronary syndromes (CCS) and obstructive coronary artery disease were selected from the multicentre ILIAS Registry. For this study, only patients with combined Doppler flow and pressure measurements were included., Results: A total of 853 patients with 1,107 vessels were included. HSR more accurately identified the presence of inducible ischaemia compared to FFR and CFR (area under the curve 0.71 vs 0.66 and 0.62, respectively; p<0.005 for both). An abnormal HSR measurement was an independent and important predictor of target vessel failure at 5-year follow-up (hazard ratio 3.80, 95% confidence interval: 2.12-6.73; p<0.005). In vessels deferred from revascularisation, HSR seems to identify more accurately those vessels that may benefit from revascularisation rather than FFR and/or CFR., Conclusions: The present study affirms the theoretical advantages of the HSR index for the detection of ischaemia-Âinducing coronary lesions in a large CCS population. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry], ClinicalTrials.gov: NCT04485234).

Background: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women., Aim: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes., Methods: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men., Results: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47-0.96, p = 0.027) and men (HR 0.84, 0.74-0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men., Conclusion: The MRR seems to be equally applicable in both women and men with stable coronary artery disease., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Recently, a novel method to estimate wedge pressure (P w )-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of P w measurements. This study sought to validate the recently introduced method to estimate P w -corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the P w measurements and the derivation of P w -corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for P w measurements was validated by estimating the coronary fractional flow reserve (FFR cor ) from myocardial fractional flow reserve (FFR myo ) in a Doppler-derived study population ( N = 53). From these patients, 24 had hyperemic P w measurements available for the evaluation of hyperemic conditions on the derivation of P w and its effect on the derivation of both "true" (with measured P w ) and "estimated" P w -corrected HMR. Nonhyperemic P w differed significantly from P w measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFR cor and FFR myo in nonhyperemic conditions ( R 2 = 0.91, P < 0.005), as well as in hyperemic conditions ( R 2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic ( R 2 = 0.86, P < 0.005) or hyperemic conditions ( R 2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic P w -corrected HMR and apparent HMR ( R 2 = 0.67, P < 0.005), hyperemic P w -corrected HMR showed a strong agreement with apparent HMR ( R 2 = 0.88, P < 0.005). We validated the calculation method for P w -corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of P w and the derivation of P w -corrected HMR. NEW & NOTEWORTHY The following are what is known: 1 ) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2 ) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1 ) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2 ) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Background and Aims: The management of chronic coronary syndrome (CCS) is informed by studies predominantly including men. This study investigated the relationship between patients sex and different endotypes of CCS, including sex-specific clinical outcomes., Methods: In patients with CCS undergoing coronary angiography, invasive Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) were measured. Patients were stratified into groups: 1) obstructive coronary artery disease (oCAD) (FFR≤0.80, no revascularization), 2) undergoing revascularization, 3) non-obstructive coronary artery disease with coronary microvascular dysfunction (CMD) (FFR>0.80, CFR≤2.5), and 4) non-obstructive coronary artery disease without CMD (FFR>0.80 and CFR>2.5)., Results: 1836 patients (2335 vessels) were included, comprising 1359 (74.0%) men and 477 (26.0%) women. oCAD was present in 14.1% and was significantly less prevalent in women than in men (10.3% vs 15.5%, respectively p < 0.01). Revascularization was present in 30.9% and was similarly prevalent in women and men (28.2% vs. 31.9%, respectively p = 0.13). CMD was present in 24.2% and was significantly more prevalent in women than men (28.6% vs 22.6%, respectively p < 0.01). Normal invasive measurements were found in 564 patients (33.0% women vs 30.0% men, p = 0.23). Male sex was associated with an increased risk of target vessel failure compared to women (HR.1.89, 95% CI 1.12-3.18, p = 0.018), regardless of CCS-endotype., Conclusions: Sex differences exist in the prevalence and outcomes of different endotypes of CCS in symptomatic patients undergoing invasive coronary angiography. In particular, oCAD (and subsequent revascularization) were more prevalent in men. Conversely, CMD was more prevalent in women. Overall, men experienced a worse cardiovascular outcome compared to women, independent of any specific CCS endotype., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR., Methods and Results: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef.-2.88, 95% confidence interval (CI): -3.05--2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75)., Conclusion: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Coronary microvascular dysfunction (CMD) is an important contributor to angina syndromes. Recently, two distinct endotypes were identified using combined assessment of coronary flow reserve (CFR) and minimal microvascular resistance (MR), termed structural and functional CMD., Aims: We aimed to assess the relevance of the combined assessment of CFR and MR in patients with angina and no obstructive coronary arteries., Methods: Patients with chronic coronary syndromes (CCS) and non-obstructive coronary artery disease (fractional flow reserve [FFR] ≥0.80) were selected (N=1,102). Functional CMD was defined as abnormal CFR in combination with normal MR and structural CMD as abnormal CFR with abnormal MR. Clinical endpoints were the incidence of major adverse cardiac events (MACE) and target vessel failure (TVF) at 5-year follow-up., Results: Abnormal CFR was associated with an increased risk of MACE and TVF at 5-year follow-up. Microvascular resistance parameters were not associated with MACE or TVF at 5-year follow-up. The risk of MACE and TVF at 5-year follow-up was similarly increased for patients with structural or functional CMD compared with patients with normal microvascular function. There were no differences between both endotypes (p=0.88 for MACE, and p=0.55 for TVF)., Conclusions: Coronary microvascular dysfunction, identified by an impaired CFR, was unequivocally associated with increased MACE and TVF rates over a 5-year follow-up period. In contrast, impaired MR was not associated with 5-year adverse clinical events. Moreover, there was no significant difference in the risk of MACE and TVF between a low CFR accompanied by pathologically increased MR (structural CMD) or not (functional CMD)., Clinicaltrials: gov: NCT04485234.

Aims: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making., Methods and Results: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R 2  = 0.757, p < 0.001). There was no correlation between respiratory rate and variations in resting Pd/Pa. When single-beat averages were used to calculate FFR, mean ΔFFR was 0.04 ± 0.02. With averaging of FFR over three or five cardiac cycles, mean ΔFFR decreased to 0.02 ± 0.02, and 0.01 ± 0.01, respectively. Using a FFR ≤ 0.80 threshold, stenosis classification changed in 20.5% (8/39), 12.8% (5/39) and 5.1% (2/39) for single-beat, three-beat and five-beat averaged FFR. The impact of respiration was more pronounced in patients with pulmonary disease (ΔFFR 0.05 ± 0.02 vs 0.03 ± 0.02, p = 0.021)., Conclusion: Beat-to-beat variations in FFR during plateau hyperemia related to respiration are common, of clinically relevant magnitude, and frequently lead FFR to cross treatment thresholds. A five-beat averaged FFR, overcomes clinically relevant impact of FFR variation., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)