Impact of Anatomical and Viability-guided Completeness of Revascularization on Clinical Outcomes in Ischemic Cardiomyopathy.

BACKGROUND: Complete revascularization of coronary disease has been linked to improved outcomes in patients with preserved left ventricular (LV) function. OBJECTIVES: To identify the impact of complete revascularization in patients with severe LV dysfunction. METHODS: Patients enrolled in the REVIVED-BCIS2 trial were eligible if baseline/procedural angiograms and viability studies were available for analysis by independent core laboratories. Anatomical and viability-guided completeness of revascularization were measured by the coronary and myocardial revascularization indices (RIcoro and RImyo) respectively, where RIcoro=[change in BCIS Jeopardy Score (BCIS-JS)] / [baseline BCIS-JS] and RImyo=[number of revascularized viable segments] / [ number of viable segments supplied by diseased vessels]. The PCI group was classified as having complete or incomplete revascularization by median RIcoro and RImyo. The primary outcome was death or hospitalization for heart failure. RESULTS: Of 700 randomized patients, 670 were included. The baseline BCIS-JS and SYNTAX scores were 8 (6 to 10) and 22 (15 to 29) respectively. In those assigned to PCI, median RIcoro and RImyo values were 67% and 85%. Compared to the group assigned to optimal medical therapy alone, there was no difference in the likelihood of the primary outcome in those receiving complete anatomical or viability-guided revascularization (HR 0.90, 95% CI 0.62-1.32 and HR 0.95, 95% CI 0.66-1.35 respectively). A sensitivity analysis by residual SYNTAX score showed no association with outcome. CONCLUSIONS: In patients with severe left ventricular dysfunction, neither complete anatomical nor viability-guided revascularization were associated with improved event-free survival compared to incomplete revascularization or treatment with medical therapy alone.

Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial.

BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 µg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890.

Interventional Diagnostic Procedure: a Practical Guide for the Assessment of Coronary Vascular Function.

Approximately 40% of patients undergoing invasive coronary angiography for investigation of angina are found to have no obstructive coronary artery disease (ANOCA). Abnormal coronary function underlies coronary vasomotion syndromes including coronary endothelial dysfunction, microvascular angina, vasospastic angina, post-PCI angina and myocardial infarction with no obstructive coronary arteries (MINOCA). Each of these endotypes are distinct subgroups, characterized by specific disease mechanisms. Diagnostic criteria and linked therapy for these conditions are now established by expert consensus and clinical guidelines. Coronary function tests are performed as an adjunctive interventional diagnostic procedure (IDP) in appropriately selected patients during coronary angiography. This aids differentiation of patients according to endotype. The IDP includes two distinct components: a diagnostic guidewire test and a pharmacological coronary reactivity test. The tests last approximately 5 minutes for the former and 10-15 minutes for the latter. Patient safety and staff education are key. The diagnostic guidewire test measures parameters of coronary flow limitation (fractional flow reserve [FFR], coronary flow reserve [CFR], microvascular resistance [index of microvascular resistance (IMR)], basal resistance index, and vasodilator function [CFR, resistive reserve ratio (RRR)]). The pharmacological coronary reactivity test measures the vasodilator potential and propensity to vasospasm of both the main coronary arteries and the micro-vessels. It involves intra-coronary infusion of acetylcholine and glyceryl trinitrate (GTN). Acetylcholine is not licensed for parenteral use and is therefore prescribed on a named-patient basis. Vasodilatation is the normal, expected response to infusion of physiological concentrations of acetylcholine. Vascular spasm represents an abnormal response, which supports the diagnosis of vasospastic angina. The purpose of this practical guide is to provide information on the preparation and administration of the IDP in clinical practice. It discusses some key preparation and safety considerations, as well as tips for procedural success. The IDP supports stratified medicine for a personalized approach to health and wellbeing.

Intravascular lithotripsy for treatment of calcific coronary lesions in ST elevation myocardial infarction.

AIMS: To describe the utility and safety of intravascular lithotripsy (IVL) in the setting of primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: We performed a retrospective analysis, across six UK sites of all patients in whom IVL was used for coronary calcium modification of the culprit lesion during primary PCI for STEMI. The 72 patients were included. IVL was used in de-novo culprit lesions in 57 (79%) of cases and culprit in-stent restenoses in 11 (15%) of cases. In four cases (6%) it was used in a newly deployed stent when this was under-expanded due to inadequate calcium modification. Of the 30 cases in which intracoronary imaging was available for stent analysis, the average stent expansion was 104%. Intra-procedural stent thrombosis occurred in one case (1%), and no-reflow in three cases (4%). The 30 day MACE rates were 18%. CONCLUSION: IVL appears to be feasible and safe for use in the treatment of calcific coronary artery disease in the setting of STEMI.

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. Objective: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. Design, Setting, and Participants: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. Main Outcomes and Measures: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. Results: Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). Conclusions and Relevance: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.

Chest pain without obstructive coronary artery disease: a case series.

BACKGROUND: Ischaemic heart disease is a leading cause of mortality in women. Even in those without obstructive coronary artery disease (CAD), women with angina continue to have increased mortality. There are gender differences in prevalence of different pathophysiologies, including functional disorders such as microvascular and vasospastic angina. CASE SUMMARY: We describe four cases of angina in women with no obstructive CAD, in whom coronary function testing was performed. These four patients were diagnosed with disorders of coronary vasomotion, including vasospastic angina and different endotypes of microvascular angina. DISCUSSION: This case series highlights the different mechanisms of ischaemia in the absence of obstructive CAD. Patients with angina and no obstructive CAD classified by computed tomography coronary angiography may have myocardial ischaemia due to microvascular angina, vasospastic angina, or both. Conventional investigations risk under-diagnosing, and as a consequence under-treating, patients with these conditions. Coronary function testing, in the form of diagnostic guidewire-based tests and adjunctive acetylcholine provocation, has proven to be critical in the accurate diagnoses and appropriate management of these patients.

Coronary microvascular dysfunction in stable ischaemic heart disease (non-obstructive coronary artery disease and obstructive coronary artery disease).

Diffuse and focal epicardial coronary disease and coronary microvascular abnormalities may exist side-by-side. Identifying the contributions of each of these three players in the coronary circulation is a difficult task. Yet identifying coronary microvascular dysfunction (CMD) as an additional player in patients with coronary artery disease (CAD) may provide explanations of why symptoms may persist frequently following and why global coronary flow reserve may be more prognostically important than fractional flow reserve measured in a single vessel before percutaneous coronary intervention. This review focuses on the challenges of identifying the presence of CMD in the context of diffuse non-obstructive CAD and obstructive CAD. Furthermore, it is going to discuss the pathophysiology in this complex situation, examine the clinical context in which the interaction of the three components of disease takes place and finally look at non-invasive diagnostic methods relevant for addressing this question.

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study.

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). OBJECTIVES: Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. DESIGN: A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. VALUE: CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population.

Sex differences in procedural and clinical outcomes following rotational atherectomy.

AIM: Evaluate sex differences in procedural net adverse clinical events and long-term outcomes following rotational atherectomy (RA). METHODS AND RESULTS: From August 2010 to 2016, 765 consecutive patients undergoing RA PCI were followed up for a median of 4.7 years. 285 (37%) of subjects were female. Women were older (mean 76 years vs. 72 years; p < .001) and had more urgent procedures (64.6 vs. 47.3%; p < .001). Females received fewer radial procedures (75.1 vs. 85.1%; p < .001) and less intravascular imaging guidance (16.8 vs. 25.0%; p = .008). After propensity score adjustment, the primary endpoint of net adverse cardiac events (net adverse clinical events: all-cause death, myocardial infarction, stroke, target vessel revascularization plus any procedural complication) occurred more often in female patients (15.1 vs. 9.0%; adjusted OR 1.81 95% CI 1.04-3.13; p = .037). This was driven by an increased risk of procedural complications rather than procedural major adverse cardiac events (MACE). Specifically, women were more likely to experience coronary dissection (4.6 vs. 1.3%; p = .008), cardiac tamponade (2.1 vs. 0.4%; p = .046) and significant bleeding (BARC ≥2: 5.3 vs. 2.3). Despite this, overall MACE-free survival was similar between males and females (adjusted HR 1.03; 95% CI 0.80-1.34; p = .81). Procedural complications during RA were associated with almost double the incidence of MACE at long-term follow-up (HR 1.92; 95% CI 1.34-2.77; p < .001). CONCLUSION: Women may be at greater risk of procedural complications following rotational atherectomy. These include periprocedural bleeding episodes and coronary perforation leading to cardiac tamponade. Despite this, the adjusted overall long-term survival free of major adverse cardiac events was similar between males and females.

1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA).

OBJECTIVES: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease. BACKGROUND: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease. METHODS: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure-facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up. RESULTS: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803). CONCLUSIONS: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294).

Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders.

BACKGROUND: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA). METHODS: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3-3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P<0.001) but with lower cardiovascular risk scores (ASSIGN score median 20% versus 24%; P=0.003). INOCA subjects had similar burden of angina (Seattle Angina Questionnaire) but reduced quality of life compared with coronary artery disease; subjects (EQ5D-5 L index 0.60 versus 0.65 units; P=0.041). RESULTS: An interventional diagnostic procedure with reference invasive tests including coronary flow reserve, microvascular resistance, and vasomotor responses to intracoronary acetylcholine (vasospasm provocation) was performed in 151 INOCA subjects. Overall, 78 (52%) had isolated microvascular angina, 25 (17%) had isolated vasospastic angina, 31 (20%) had both, and 17 (11%) had noncardiac chest pain. Regression analysis showed inducible ischemia on treadmill testing (OR, 7.5 [95% CI, 1.7-33.0]; P=0.008) and typical angina (OR, 2.7 [1.1-6.6]; P=0.032) were independently associated with microvascular angina. Female sex tended to associate with a diagnosis of microvascular angina although this was not significant (OR, 2.7 [0.9-7.9]; P=0.063). Vasospastic angina was associated with smoking (OR, 9.5 [2.8-32.7]; P<0.001) and age (OR, 1.1 per year, [1.0-1.2]; P=0.032]. CONCLUSIONS: Over three quarters of patients with INOCA have identifiable disorders of coronary vasomotion including microvascular and vasospastic angina. These patients have comparable angina burden but reduced quality of life compared to patients with obstructive coronary artery disease. Microvascular angina and vasospastic angina are distinct disorders that may coexist but differ in associated clinical characteristics, symptoms, and angina severity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193294.

Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. METHODS: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). RESULTS: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. CONCLUSIONS: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.

BACKGROUND: Patients with angina symptoms and/or signs of ischemia but no obstructive coronary artery disease (INOCA) pose a diagnostic and therapeutic challenge. OBJECTIVES: The purpose of this study was to test whether an interventional diagnostic procedure (IDP) linked to stratified medicine improves health status in patients with INOCA. METHODS: The authors conducted a randomized, controlled, blinded clinical trial of stratified medical therapy versus standard care in patients with angina. Patients with angina undergoing invasive coronary angiography (standard care) were recruited. Patients without obstructive CAD were immediately randomized 1:1 to the intervention group (stratified medical therapy) or the control group (standard care, IDP sham procedure). The IDP consisted of guidewire-based assessment of coronary flow reserve, index of microcirculatory resistance, fractional flow reserve, followed by vasoreactivity testing with acetylcholine. The primary endpoint was the mean difference in angina severity at 6 months (assessed by the Seattle Angina Questionnaire summary score). RESULTS: A total of 391 patients were enrolled between November 25, 2016, and November 12, 2017. Coronary angiography revealed obstructive disease in 206 (53.7%). One hundred fifty-one (39%) patients without angiographically obstructive CAD were randomized (n = 76 intervention group; n = 75 blinded control group). The intervention resulted in a mean improvement of 11.7 U in the Seattle Angina Questionnaire summary score at 6 months (95% confidence interval [CI]: 5.0 to 18.4; p = 0.001). In addition, the intervention led to improvements in the mean quality-of-life score (EQ-5D index 0.10 U; 95% CI: 0.01 to 0.18; p = 0.024) and visual analogue score (14.5 U; 95% CI: 7.8 to 21.3; p < 0.001). There were no differences in major adverse cardiac events at the 6-month follow-up (2.6% controls vs. 2.6% intervention; p = 1.00). CONCLUSIONS: Coronary angiography often fails to identify patients with vasospastic and/or microvascular angina. Stratified medical therapy, including an IDP with linked medical therapy, is routinely feasible and improves angina in patients with no obstructive CAD. (CORonary MICrovascular Angina [CorMicA]; NCT03193294).

Systemic microvascular dysfunction in microvascular and vasospastic angina.

Aims: Coronary microvascular dysfunction and/or vasospasm are potential causes of ischaemia in patients with no obstructive coronary artery disease (INOCA). We tested the hypothesis that these patients also have functional abnormalities in peripheral small arteries. Methods and results: Patients were prospectively enrolled and categorised as having microvascular angina (MVA), vasospastic angina (VSA) or normal control based on invasive coronary artery function tests incorporating probes of endothelial and endothelial-independent function (acetylcholine and adenosine). Gluteal biopsies of subcutaneous fat were performed in 81 subjects (62 years, 69% female, 59 MVA, 11 VSA, and 11 controls). Resistance arteries were dissected enabling study using wire myography. Maximum relaxation to ACh (endothelial function) was reduced in MVA vs. controls [median 77.6 vs. 98.7%; 95% confidence interval (CI) of difference 2.3-38%; P = 0.0047]. Endothelium-independent relaxation [sodium nitroprusside (SNP)] was similar between all groups. The maximum contractile response to endothelin-1 (ET-1) was greater in MVA (median 121%) vs. controls (100%; 95% CI of median difference 4.7-45%, P = 0.015). Response to the thromboxane agonist, U46619, was also greater in MVA (143%) vs. controls (109%; 95% CI of difference 13-57%, P = 0.003). Patients with VSA had similar abnormal patterns of peripheral vascular reactivity including reduced maximum relaxation to ACh (median 79.0% vs. 98.7%; P = 0.03) and increased response to constrictor agonists including ET-1 (median 125% vs. 100%; P = 0.02). In all groups, resistance arteries were ≈50-fold more sensitive to the constrictor effects of ET-1 compared with U46619. Conclusions: Systemic microvascular abnormalities are common in patients with MVA and VSA. These mechanisms may involve ET-1 and were characterized by endothelial dysfunction and enhanced vasoconstriction. Clinical trial registration: ClinicalTrials.gov registration is NCT03193294.