Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing.

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina with no obstructive coronary arteries in patients. Both can be diagnosed by invasive coronary function testing (ICFT) using acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared with a 1-minute ACh bolus injection protocol in testing CED and CAS. We evaluated 220 consecutive patients with angina and no obstructive coronary arteries who underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion, and thereafter 110 patients using 1-minute bolus injections, because of a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low-dose ACh and CAS according to the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%, p = 0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3 vs 1-minute protocol (24% vs 44%, p = 0.004). Including T-wave abnormalities in the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as a diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as a diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.

Impact of coronary hyperemia on collateral flow correction of coronary microvascular resistance indices.

Recently, a novel method to estimate wedge pressure (Pw)-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 Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-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.

ANOCA patients with and without coronary vasomotor dysfunction present with limited electrocardiographic remodeling.

Background: Coronary vasomotor dysfunction (CVDys) comprises coronary vasospasm (CVS) and/or coronary microvascular dysfunction (CMD) and is highly prevalent in patients with angina and non-obstructive coronary artery disease (ANOCA). Invasive coronary function testing (CFT) to diagnose CVDys is becoming more common, enabling pathophysiologic research of CVDys. This study aims to explore the electrophysiological characteristics of ANOCA patients with CVDys. Methods: We collected pre-procedural 12-lead electrocardiograms of ANOCA patients with CVS (n = 35), CMD (n = 24), CVS/CMD (n = 26) and patients without CVDys (CFT-, n = 23) who participated in the NL-CFT registry and underwent CFT. Heart axis and conduction times were compared between patients with CVS, CMD or CVS/CMD and patients without CVDys. Results: Heart axis, heart rate, PQ interval and QRS duration were comparable between the groups. A small prolongation of the QT-interval corrected with Bazett (QTcB) and Fridericia (QTcF) was observed in patients with CVDys compared to patients without CVDys (CVS vs CFT-: QTcB = 422 ± 18 vs 414 ± 18 ms (p = 0.14), QTcF = 410 ± 14 vs 406 ± 12 ms (p = 0.21); CMD vs CFT-: QTcB = 426 ± 17 vs 414 ± 18 ms (p = 0.03), QTcF = 413 ± 11 vs 406 ± 12 ms (p = 0.04); CVS/CMD vs CFT-: QTcB = 424 ± 17 vs 414 ± 18 ms (p = 0.05), QTcF = 414 ± 14 vs 406 ± 12 ms (p = 0.04)). Conclusions: Pre-procedural 12-lead electrocardiograms were comparable between patients with and without CVDys undergoing CFT except for a slightly longer QTc interval in patients with CVDys compared to patients without CVDys, suggesting limited cardiac remodeling in patients with CVDys.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Impact of sex on the assessment of the microvascular resistance reserve.

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.

Prognostic Implications of Individual and Combinations of Resting and Hyperemic Coronary Pressure and Flow Parameters.

Background: Coronary pressure- and flow-derived parameters have prognostic value. Objectives: This study aims to investigate the individual and combined prognostic relevance of pressure and flow parameters reflecting resting and hyperemic conditions. Methods: A total of 1,971 vessels deferred from revascularization after invasive pressure and flow assessment were included from the international multicenter registry. Abnormal resting pressure and flow were defined as distal coronary pressure/aortic pressure ≤0.92 and high resting flow (1/resting mean transit time >2.4 or resting average peak flow >22.7 cm/s), and abnormal hyperemic pressure and flow as fractional flow reserve ≤0.80 and low hyperemic flow (1/hyperemic mean transit time <2.2 or hyperemic average peak flow <25.0 cm/s), respectively. The clinical endpoint was target vessel failure (TVF), myocardial infarction (MI), or cardiac death at 5 years. Results: The mean % diameter stenosis was 46.8% ± 16.5%. Abnormal pressure and flow were independent predictors of TVF and cardiac death/MI (all P < 0.05). The risk of 5-year TVF or MI/cardiac death increased proportionally with neither, either, and both abnormal resting pressure and flow, and abnormal hyperemic pressure and flow (all P for trend < 0.001). Abnormal resting pressure and flow were associated with a higher rate of TVF or MI/cardiac death in vessels with normal fractional flow reserve; this association was similar for abnormal hyperemic pressure and flow in vessels with normal resting distal coronary pressure/aortic pressure (all P < 0.05). Conclusions: Abnormal resting and hyperemic pressure and flow were independent prognostic predictors. The abnormal flow had an additive prognostic value for pressure in both resting and hyperemic conditions with complementary prognostic between resting and hyperemic parameters.

Prognostic Value of Histopathological Thrombus Age in Large Vessel Occlusion-Related Stroke.

INTRODUCTION: Acute mechanical thrombectomy (MT) is the preferred treatment for large vessel occlusion-related stroke. Histopathological research on the obtained occlusive embolic thrombus may provide information regarding the aetiology and pathology of the lesion to predict prognosis and propose possible future acute ischaemic stroke therapy. METHODS: A total of 75 consecutive patients who presented to the Amphia Hospital with acute large vessel occlusion-related stroke and underwent MT were included in the study. The obtained thrombus materials were subjected to standard histopathological examination. Based on histological criteria, they were considered fresh (<1 day old) or old (>1 day old). Patients were followed for 2 years for documentation of all-cause mortality. RESULTS: Thrombi were classified as fresh in 40 patients (53%) and as older in 35 patients (47%). Univariate Cox regression analysis showed that thrombus age, National Institutes of Health Stroke Scale at hospital admission, and patient age were associated with long-term mortality (p < 0.1). Multivariable Cox hazards and Kaplan-Meier analysis demonstrated that after extensive adjustment for clinical and procedural variables, thrombus age persisted in being independently associated with higher long-term mortality (hazard ratio: 3.34; p = 0.038, log-rank p = 0.013). CONCLUSION: In this study, older thromboemboli are responsible for almost half of acute large ischaemic strokes. Moreover, the presence of an old thrombus is an independent predictor of mortality in acute large vessel occlusion-related stroke. More research is warranted regarding future therapies based on thrombus composition.

Prognostic Value of Modified Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging.

BACKGROUND: Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [15O]H2O positron emission tomography perfusion imaging. METHODS: Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction. RESULTS: During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; P<0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; P=0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; P=0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; P<0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; P=0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; P<0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall P=0.017). CONCLUSIONS: [15O]H2O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [15O]H2O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome.

Sex differences in prevalence and outcomes of the different endotypes of chronic coronary syndrome in symptomatic patients undergoing invasive coronary angiography: Insights from the global ILIAS invasive coronary physiology registry.

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.

Development of artificial intelligence tools for invasive Doppler-based coronary microvascular assessment.

Aims: Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity. Methods and results: A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman's rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias -1.68 cm/s, 95% confidence interval (CI) -2.13 to -1.23 cm/s, P < 0.001 with limits of agreement (LOA) -4.03 to 0.68 cm/s; console flow vs. expert flow bias -2.63 cm/s, 95% CI -3.74 to -1.52, P < 0.001, 95% LOA -8.45 to -3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console). Conclusion: An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment.

Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study.

Background: Treatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment. Methods: Patients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase. Results: 28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (duration*severity: -9 [-134 78] vs -45 [-353 11], p = 0.136 and frequency*severity: -1.7 [-5.8 1.2] vs -1.8 [-6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo. Conclusion: In patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.

Changes in microvascular resistance following percutaneous coronary intervention - From the ILIAS global registry.

BACKGROUND: Microvascular resistance (MR) has prognostic value in acute and chronic coronary syndromes following percutaneous coronary intervention (PCI), however anatomic and physiologic determinants of the relative changes of MR and its association to target vessel failure (TVF) has not been investigated previously. This study aims to evaluate the association between changes in MR and TVF. METHODS: This is a sub-study of the Inclusive Invasive Physiological Assessment in Angina Syndromes (ILIAS) registry which is a global multi-centre initiative pooling lesion-level coronary pressure and flow data. RESULTS: Paired pre-post PCI haemodynamic data were available in n = 295 vessels out of n = 828 PCI treated patients and of these paired data on MR was present in n = 155 vessels. Vessels were divided according to increase vs. decrease % in microvascular resistance following PCI (ΔMR % ≤ 0 vs. ΔMR > 0%). Decreased microvascular resistance ΔMR % ≤ 0 occurred in vessels with lower pre-PCI fractional flow reserve (0.67 ± 0.15 vs. 0.72 ± 0.09 p = 0.051), coronary flow reserve (1.9 ± 0.8 vs. 2.6 ± 1.8 p < 0.0001) and higher hyperemic microvascular resistance (2.76 ± 1.3 vs. 1.62 ± 0.74 p = 0.001) and index of microvascular resistance (24.4 IQ (13.8) vs. 15. 8 IQ (13.2) p = 0.004). There was no difference in angiographic parameters between ΔMR % ≤ 0 vs. ΔMR > 0%. In a cox regression model ΔMR % > 0 was associated with increased rate of TVF (hazard ratio 95% CI 3.6 [1.2; 10.3] p = 0.018). CONCLUSION: Increased MR post-PCI was associated with lesions of less severe hemodynamic influence at baseline and higher rates of TVF at follow-up.

Practical Approach for Angina and Non-Obstructive Coronary Arteries: A State-of-the-Art Review.

Anginal symptoms are frequently encountered in patients without the presence of significant obstructive coronary artery disease (CAD). It is increasingly recognized that vasomotor disorders, such as an abnormal vasodilatory capacity of the coronary microcirculation or coronary vasospasm, are the dominant pathophysiological substrate in these patients. Although the evidence with respect to angina in patients with non-obstructive coronary arteries is accumulating, the diagnosis and treatment of these patients remains challenging. In this review, we aimed to provide a comprehensive overview regarding the pathophysiological origins of angina with non-obstructive coronary arteries disorders and its diagnostic and therapeutic considerations. Hereby, we provide a practical approach for the management of patents with angina and non-obstructive CAD.

Fractional flow reserve use in coronary artery revascularization: A systematic review and meta-analysis.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is recommended in revascularization guidelines for intermediate lesions. However, recent studies comparing FFR-guided PCI with non-physiology-guided revascularization have reported conflicting results. PubMed and Embase were searched for studies comparing FFR-guided PCI with non-physiology-guided revascularization strategies (angiography-guided, intracoronary imaging-guided, coronary artery bypass grafting). Data were pooled by meta-analysis using random-effects model. 26 studies enrolling 78,897 patients were included. FFR-guided PCI as compared to non-physiology-guided coronary revascularization had lower risk of all-cause mortality (odds ratio [OR] 0.79 95% confidence interval [CI] 0.64-0.99, I2 = 53%) and myocardial infarction (MI) (OR 0.74 95% CI 0.59-0.93, I2 = 44.7%). However, no differences between groups were found in terms of major adverse cardiac events (MACEs) (OR 0.86 95% CI 0.72-1.03, I2 = 72.3%) and repeat revascularization (OR 1 95% CI 0.82-1.20, I2 = 43.2%). Among patients with coronary artery disease (CAD), FFR-guided PCI as compared to non-physiology-guided revascularization was associated with a lower risk of all-cause mortality and MI.

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: Rationale and design of the LEGACY study.

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.

Post-spastic flow recovery time to document vasospasm induced ischemia during acetylcholine provocation testing.

Background: Intracoronary acetylcholine (ACh) provocation is an established method for diagnosing epicardial and microvascular vasospasm in contemporary clinical practice. We hypothesize that ACh-induced vasospasm is followed by post-spastic reactive hyperemia (PSRH), which is measured as an increased flow-recovery time. Objectives: To assess flow-recovery time, indicative of ischemia, among the diagnostic endotypes that follow ACh provocation testing. Methods: Patients with angina and non-obstructive coronary artery disease on angiography who underwent ACh provocation testing were included in this analysis. Doppler flow was continuously measured during the procedure and used to determine the flow-recovery time, which was calculated as time between cessation of ACh infusion and the point of flow recovery. Results: Conventional provocation testing according to the COVADIS criteria diagnosed vasospasm in 63%(77/123), an equivocal result in 22%(27/123) and a negative result in 15%(19/123) of patients. In reaction to the highest-dose of ACh, flow-recovery time was significantly extended and similar in the epicardial, microvascular and equivocal test results compared to the negative result (all p < 0.001) indicative of PSRH. Conclusion: Flow-recovery time in patients with an equivocal result is similar to patients with vasospasm, which indicates the occurrence of myocardial ischemia and therefore, these patients may benefit from medical treatment.

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry.

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.