Abstract Background In the SENIOR-RITA trial, among older adults with non-ST-elevation myocardial infarction (NSTEMI), an invasive strategy did not reduce the composite outcome of cardiovascular death or non-fatal myocardial infarction compared with a conservative strategy over a median follow-up of 4.1 years. Objectives To describe the angiographic characteristics of patients randomized to the invasive arm. Methods SENIOR-RITA was a prospective, multicentre, randomized controlled trial recruiting NSTEMI patients aged ≥75 years. From November 2016 to March 2023, 1518 patients from 48 UK sites were randomized 1:1 to an invasive or conservative strategy. Procedural data were collected, and angiographic data were analysed using quantitative coronary angiography (QCA) at Newcastle University angiographic core laboratory using QAngio® XA Medis. Results Of 680 patients undergoing angiography, QCA analysis was performed in 667 participants. Obstructive coronary artery disease was found in 76.8%, and 13% had prior coronary surgical revascularization. A total of 1173 lesions were identified. Most lesions (29.5%) were classified as type B2 according to the ACC/AHA classification. Lesions in patients not receiving percutaneous coronary intervention (PCI) were angiographically more complex than those treated with PCI, with higher prevalence of type C lesions, bifurcation, ostial lesions, and presence of collaterals. Overall, 330 patients (49.5%) underwent PCI, which was successful in 96.5% with minimal complications. Conclusions The SENIOR-RITA angiography sub-study is the largest subgroup analysis to date in older NSTEMI adults providing important insights into the angiographic characteristics and emphasising the importance of a holistic patient-centred care for older adults.

Background The relationship between atherosclerosis and endotypes of myocardial ischaemia with no obstructive coronary artery disease (INOCA) is unclear. We investigated potential associations between cumulative atherosclerotic plaque burden quantified using the Gensini score, novel invasive indices of coronary microvascular function (microvascular resistance reserve (MRR); resistive reserve ratio (RRR)) and related INOCA endotypes.Methods Coronary angiography and invasive coronary function tests were simultaneously acquired in the CorMicA cohort. A comprehensive physiological assessment was performed using both a thermodilution-based diagnostic guidewire and intracoronary acetylcholine provocation testing. Angiograms were examined for luminal stenosis in each segment of the SYNTAX coronary model. Cumulative plaque burden was quantified using the Gensini score, which incorporated both the number of diseased coronary segments and stenosis severity. Results were compared with indices of microvascular function and INOCA endotypes. Angiographic analyses were performed blind to coronary physiology findings.Results In 151 participants (median age 61 years; 73.5% female) without flow-limiting coronary artery disease, medical history included 41.7% smoking, 63.6% hypertension and 19.2% diabetes mellitus. The left anterior descending artery underwent diagnostic guidewire testing in 85.4%, and 55.0% of participants had abnormal coronary flow reserve (CFR) and/or Index of Microcirculatory Resistance (IMR). The median Gensini score was 6.0 (IQR 2.5-11.0). CFR (p=0.012), MRR (p=0.026) and RRR (p=0.026), but not IMR (p=0.445), were univariably associated with raised Gensini scores. These significant effects persisted in multivariable models controlling for potential confounders. Considering INOCA endotypes, Gensini scores differed among participants with microvascular angina (MVA) (7.0 (2.5-11.0)), vasospastic angina (VSA) (4.5 (2.0-10.0)), mixed MVA/VSA (9.0 (5.0-11.5)) and non-cardiac symptoms (3.5 (1.5-8.0)); Kruskal-Wallis p=0.030.Conclusions Reduced CFR, MRR and RRR, and MVA were associated with increased coronary atherosclerotic plaque burden, as evidenced by higher Gensini scores. These novel findings provide a mechanistic link between INOCA and cardiovascular events, reinforcing the importance of antiatherosclerosis therapy in patients with MVA.

IntroductionMyocardial infarction with no obstructive coronary arteries (MINOCA) occurs in approximately 1 in 9 presentations with acute coronary syndrome. Cardiac MRI is guideline indicated in the investigation of aetiology for MINOCA which includes a spectrum of pathophysiology, for which there is no evidence-based therapy. The presence of ischaemic late gadolinium enhancement is prognostic in myocardial infarction and represents irreversible myocardial damage. However, factors predicting the likelihood of ischaemic late gadolinium enhancement in patients with MINOCA are unclear.Materials and MethodsThe overall aim is to undertake a prospective, registry-based clinical trial in MINOCA [NCT05198791]. Specific aims (1) assess the feasibility of enrolling patients during acute NHS care into a therapeutic trial, (2) in all-comers (registry), undertake multisystem phenotyping using objective, quantitative methods, (3) in patients stratified by invasive evidence of coronary microvascular dysfunction (PressureWire XTM, Abbott), randomise (1:1) to a vasculo-protective intervention (eplerenone 25–50 mg daily for 6 months) or treatment as usual, (4) quantify NT-proBNP (primary outcome, trial), patient reported outcome measures and clinical outcomes at baseline, 30 days and 6 months. Cardiac function and pathology are assessed (<14 days) using multiparametric cardiac MRI (CMR, Siemens AVANTO 1.5T). Late gadolinium enhancement (LGE) patterns are described as ischaemic (sub-endocardial, transmural), non-ischaemic (mid-wall, epicardial), non-pathological (insertion point, septal artery) or no LGE.ResultsOf 82 patients with CMR data recruited between May 2022 and September 2023 (mean age (SD): 60 (11) years; female (%): 78 (63%), 26 (32%) had ischaemic LGE, 6 (7%) non-ischaemic LGE and 34 (41%) no LGE. Factors associated with ischaemic LGE (vs. non-ischaemic vs. no LGE) included ST-elevation at presentation, left ventricular ejection fraction <55%, lower invasive coronary flow reserve (ischaemic LGE: 3.6 (1.8) vs. non-ischaemic LGE: 6.4 (3.3), P = 0.046) and greater peak high sensitivity troponin (median [IQR] – ischaemic LGE: 804 [272, 3359] ng/L, non-ischaemic LGE: 57 [48, 404] ng/L, no LGE: 216 [56, 490] ng/L; P = 0.003).DiscussionThe presence of ischaemic LGE on CMR may help to identify patients at greater risk of adverse outcomes [PMID: 37480903]. The StratMed-MINOCA registry-based clinical trial will provide information on integrating stratified medicine within a MINOCA acute care pathway. The randomised trial will provide novel data on whether short-term (6-month) mineralocorticoid receptor antagonist therapy using eplerenone, has cardio-protective effects.ConclusionIschaemic LGE is common in MINOCA, and associated factors include coronary microvascular dysfunction, peak troponin concentration and left ventricular systolic dysfunction.AcknowledgementsRobert Sykes is supported by funding from the British Heart Foundation Centre of Research Excellence (RE/18/6/34217),NHS Greater Glasgow and Clyde Endowment Funding (GN21CA394) and Abbott Vascular. Professor Berry is supported by a British Heart Foundation Centre of Research Excellence award (RE/18/6/34217) and funding from the Chief Scientist Office, UKRI (COVID-HEART, reference MC/PC/20014), EPSRC (EP/N014642/1; EP/S030875/1) and Wellcome Trust. Andrew Morrow and Colin Berry are supported by the Medical Research Council (MR/S018905/1).

Assessing coronary physiology after stent implantation facilitates the optimisation of percutaneous coronary intervention (PCI). Coronary artery disease (CAD) patterns can be characterised by the pullback pressure gradient (PPG) index. The impact of focal vs. diffuse disease on physiology-guided incremental optimisation strategy (PIOS) is unknown. This is a sub-study of the TARGET-FFR randomized clinical trial (NCT03259815). The study protocol directed that optimisation be attempted for patients in the PIOS arm when post-PCI FFR was <0.90. Overall, 114 patients (n = 61 PIOS and 53 controls) with both pre-PCI fractional flow reserve (FFR) pullbacks and post-PCI FFR were included. A PPG ≥ 0.74 defined focal CAD. The PPG correlated significantly with post-PCI FFR (r = 0.43; 95% CI 0.26 to 0.57; p-value < 0.001) and normalised delta FFR (r = 0.49; 95% CI 0.34 to 0.62; p-value < 0.001). PIOS was more frequently applied to vessels with diffuse CAD (6% focal vs. 42% diffuse; p-value = 0.006). In patients randomized to PIOS, those with focal disease achieved higher post-PCI FFR than patients with diffuse CAD (0.93 ± 0.05 vs. 0.83 ± 0.07, p < 0.001). There was a significant interaction between CAD patterns and the randomisation arm for post-PCI FFR (p-value for interaction = 0.004). Physiology-guided stent optimisation was applied more frequently to vessels with diffuse disease; however, patients with focal CAD at baseline achieved higher post-PCI FFR.

Conflicts of Interest Professor Colin Berry is employed by The University of Glasgow, which holds research and consultancy agreements with Abbot Vascular, AstraZeneca, Coroventis, GSK, HeartFlow, Menarini, Neovasc, Novartis, Siemens Healthcare and ValoHealth. These companies had no involvement in this manuscript. The other authors do not have any potential conflicts of interest. Support Statement Professor Berry is supported by a British Heart Foundation Centre of Research Excellence award (RE/18/6134217) and funding from the Chief Scientist Office, UKRI (COVID-HEART, reference MC/PC/20014), EPSRC (EP/N014642/1; EP/S030875/1) and Wellcome Trust. Dr Andrew Morrow is supported by research funding from the Medical Research Council (MR/S018905/1). Dr Kenneth Mangion is supported by research funding from the Chief Scientist Office (COV/LTE/20/10, COV/GLA/20/05). Abstract Background Myocardial infarction and non-obstructive coronary arteries (MINOCA) affects 1 in 9 patients with acute coronary syndrome. Vascular pathophysiology includes atherothrombosis and coronary vasomotion disorders. MINOCA has an unmet therapeutic need. Objectives To implement stratified medicine in patients with MINOCA by undertaking a prospective, registry-based, randomised, blinded end-point trial. Rationale There are no evidence-based, disease-modifying therapies for patients with MINOCA. Preventive therapy with antiplatelet drugs and statins is empirical. Coronary microvascular dysfunction, including increased microvascular resistance, impaired vasodilator reserve and vasospasm, is implicated in the pathogenesis of MINOCA. Targeted therapy may reduce myocardial injury, improve myocardial recovery and health status prospectively. The rationale is for a stratified medicine approach targeting microvascular dysfunction with eplerenone, a vasculoprotective mineralocorticoid receptor antagonist, in MINOCA patients with coronary microvascular dysfunction. Design Following informed consent, 350 patients with MINOCA will be prospectively enrolled (NCT05198791) into a registry. Coronary microvascular function will be measured during invasive angiography. Eligible patients with one or more cardiovascular risk factors and elevated index of microvascular resistance (IMR ≥25) will be randomised to receive eplerenone or standard care (n = 150) in a prospective randomised open blinded end-point design. All patients will undergo the same assessments including cardiovascular magnetic resonance imaging (MRI) within two weeks of enrolment to establish a final diagnosis. Trial patients will also be invited to undergo repeat MRI with adenosine stress perfusion at six months. Primary outcome: Registry: the proportion of patients with MINOCA and IMR ≥25; Trial: Within-subject change in NT-proBNP at pre-defined measurement time-points: baseline, 1 and 6 months. Secondary outcomes Global hyperaemic myocardial blood flow (ml/min/g tissue); patient reported outcome measures and quality of life questionnaires; health-economics questionnaires, within-subject change in markers of collagen degradation as a marker of myocardial fibrosis vascular adhesion molecules as markers of vascular inflammation. Intravascular imaging with optical coherence tomography (OCT) will be undertaken in a sub-study (n=30). Participants will be invited to take part in a vascular sub-study, undergoing gluteal subcutaneous fat biopsy to isolate and characterise small resistance artery biology. Value Novel data on stratified medicine for MINOCA and eplerenone as potential disease-modifying therapy for this condition.

Background: Twenty percent to 40% of patients are affected by angina after percutaneous coronary intervention (PCI), which is associated with anxiety, depression, impaired physical function, and reduced quality of life. Understanding patient and procedural factors associated with post-PCI angina may inform alternative approaches to treatment. Methods: Two hundred thirty patients undergoing PCI completed the Seattle Angina Questionnaire (SAQ-7) and European quality of life–5 dimension–5 level (EQ-5D-5L) questionnaires at baseline and 3 months post-PCI. Patients received blinded intracoronary physiology assessments before and after stenting. A post hoc analysis was performed to compare clinical and procedural characteristics among patients with and without post-PCI angina (defined by follow-up SAQ-angina frequency score <100). Results: Eighty-eight of 230 patients (38.3%) reported angina 3 months post-PCI and had a higher incidence of active smoking, atrial fibrillation, and history of previous myocardial infarction or PCI. Compared with patients with no angina at follow-up, they had lower baseline SAQ summary scores (69.48±24.12 versus 50.20±22.59, P <0.001) and EQ-5D-5L health index scores (0.84±0.15 versus 0.69±0.22, P <0.001). Pre-PCI fractional flow reserve (FFR) was lower among patients who had no post-PCI angina (0.56±0.15 versus 0.62±0.13, P =0.003). Percentage change in FFR after PCI had a moderate correlation with angina frequency score at follow-up ( r =0.36, P <0.0001). Patients with post-PCI angina had less improvement in FFR (43.1±33.5% versus 67.0±50.7%, P <0.001). There were no between-group differences in post-PCI FFR, coronary flow reserve, or corrected index of microcirculatory resistance. Patients with post-PCI angina had lower SAQ-summary scores (64.01±22 versus 95.16±8.72, P ≤0.001) and EQ-5D-5L index scores (0.69±0.26 versus 0.91±0.17, P ≤0.001) at follow-up. Conclusions: Larger improvements in FFR following PCI were associated with less angina and better quality of life at follow-up. In patients with stable symptoms, intracoronary physiology assessment can inform expectations of angina relief and quality of life improvement after stenting and thereby help to determine the appropriateness of PCI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03259815.

The association between cardiovascular disease and diabetes is increasingly understood and shared therapeutic targets are emerging. We describe the presentation and successful management of ST-elevation myocardial infarction (STEMI) secondary to coronary thrombus in a young patient with a new diagnosis of type 2 diabetes and diabetic ketoacidosis.

In cardiogenic shock with severe left main coronary artery stenosis (LM), limited information exists on short and longer-term outcomes. We sought to determine the outcomes of unprotected LM PCI in cardiogenic shock.Excluding patients with previous CABG, consecutive patients undergoing PCI in cardiogenic shock from the Melbourne Intervention Group registry between 2005 and 2013 were analysed. Those post LM PCI were compared to those post non-LM PCI. Patient and procedural data were collected with 30-day and 12-month follow-up. Australian National Death Index linkage was performed for long-term mortality analysis.After excluding previous CABG, 18,069 procedures were performed during 1st January 2005 to 30th November 2013, 601 procedures in the setting of cardiogenic shock. Of these, 45 were performed to an isolated LM and 556 to a non-LM. Those with LM PCI were older and more likely to have a baseline left ventricular ejection fraction (LVEF) of <45%. The in-hospital, 30-day, 12-month and long-term mortality to 9 years in cardiogenic shock after LM PCI was 64.4%, 66.7%, 73.3% and 80.0% compared to 36.5%, 36.9%, 40.5% and 46.0%, after non-LM PCI (p < 0.001). On multivariate analysis, LM PCI was a significant independent predictor of long-term mortality (HR1.59, 95%CI 1.00–2.53, p = 0.048). Landmark analysis of survivors to discharge found the long-term mortality of LM PCI approaches 60% compared to 27% for those with non-LM PCI (p = 0.003).Long-term outcomes after PCI to LM in cardiogenic shock are poor, with much of the excess in mortality occurring early. However, reasonable long-term survival was found beyond the initial high-risk period.

Aims Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevation myocardial infarction (STEMI) to heart failure. Here, we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury. Methods and results We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 h post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis. Conclusion Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.

Aims A fractional flow reserve (FFR) value >= 0.90 after percutaneous coronary intervention (PCI) is associated with a reduced risk of adverse cardiovascular events. TARGET-FFR is an investigator-initiated, single-centre, randomized controlled trial to determine the feasibility and efficacy of a post-PCI FFR-guided optimization strategy vs. standard coronary angiography in achieving final post-PCI FFR values >= 0.90. Methods and results After angiographically guided PCI, patients were randomized 1:1 to receive a physiology-guided incremental optimization strategy (PIOS) or a blinded coronary physiology assessment (control group). The primary outcome was the proportion of patients with a final post-PCI FFR >= 0.90. Final FFR <= 0.80 was a prioritized secondary outcome. A total of 260 patients were randomized (131 to PIOS, 129 to control) and 68.1% of patients had an initial post-PCI FFR <0.90. In the PIOS group, 30.5% underwent further intervention (stent post-dilation and/or additional stenting). There was no significant difference in the primary endpoint of the proportion of patients with final post-PCI FFR >= 0.90 between groups (PIOS minus control 10%, 95% confidence interval -1.84 to 21.91, P = 0.099). The proportion of patients with a final FFR <= 0.80 was significantly reduced when compared with the angiography-guided control group (-11.2%, 95% confidence interval -21.87 to -0.35], P = 0.045). Conclusion Over two-thirds of patients had a physiologically suboptimal result after angiography-guided PCI. An FFR-guided optimization strategy did not significantly increase the proportion of patients with a final FFR >= 0.90, but did reduce the proportion of patients with a final FFR <= 0.80.

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.

Background: The index of microcirculatory resistance (IMR) of the infarct-related artery and left ventricular end-diastolic pressure (LVEDP) are acute, prognostic biomarkers in patients undergoing primary percutaneous coronary intervention. The clinical significance of IMR and LVEDP in combination is unknown. Methods: IMR and LVEDP were prospectively measured in a prespecified substudy of the T-TIME clinical trial (Trial of Low Dose Adjunctive Alteplase During Primary PCI). IMR was measured using a pressure- and temperature-sensing guidewire following percutaneous coronary intervention. Prognostically established thresholds for IMR (>32) and LVEDP (>18 mm Hg) were predefined. Contrast-enhanced cardiovascular magnetic resonance imaging (1.5 Tesla) was acquired 2 to 7 days and 3 months postmyocardial infarction. The primary end point was major adverse cardiac events, defined as cardiac death/nonfatal myocardial infarction/heart failure hospitalization at 1 year. Results: IMR and LVEDP were both measured in 131 patients (mean age 59±10.7 years, 103 [78.6%] male, 48 [36.6%] with anterior myocardial infarction). The median IMR was 29 (interquartile range, 17–55), the median LVEDP was 17 mm Hg (interquartile range, 12–21), and the correlation between them was not statistically significant ( r =0.15; P =0.087). Fifty-three patients (40%) had low IMR (≤32) and low LVEDP (≤18), 18 (14%) had low IMR and high LVEDP, 31 (24%) had high IMR and low LVEDP, while 29 (22%) had high IMR and high LVEDP. Infarct size (% LV mass), LV ejection fraction, final myocardial perfusion grade ≤1, TIMI (Thrombolysis In Myocardial Infarction) flow grade ≤2, and coronary flow reserve were associated with LVEDP/IMR group, as was hospitalization for heart failure (n=18 events; P =0.045) and major adverse cardiac events (n=21 events; P =0.051). LVEDP>18 and IMR>32 combined was associated with major adverse cardiac events, independent of age, estimated glomerular filtration rate, and infarct-related artery (odds ratio, 5.80 [95% CI, 1.60–21.22] P =0.008). The net reclassification improvement for detecting major adverse cardiac events was 50.6% (95% CI, 2.7–98.2; P =0.033) when LVEDP>18 was added to IMR>32. Conclusions: IMR and LVEDP in combination have incremental value for risk stratification following primary percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02257294.

Aims Endothelin-1 (ET-1) is a potent vasoconstrictor peptide [inked to vascular diseases through a common intronic gene enhancer [(rs9349379-G allele), chromosome 6 (PHACTR1/EDN1)]. We performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD). Methods and results Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects [allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P= 0.013]. The G allele was associated with higher plasma serum ET-1 [Least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10-0.53; P = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10-4.96; P = 0.027]. Muttimodatity non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5T (N= 107; GG 56%, AG 43%, AA 31%, P= 0.042) and exercise testing (N= 87;-3.0 units in Duke Exercise Treadmill Score;-5.8 to-0.1; P= 0.045). Endothetin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status. Conclusion We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina.

BackgroundSegmental extent of infarction assessed by late gadolinium enhancement (LGE) imaging early post‐ST‐segment elevation myocardial infarction (STEMI) has utility in predicting left ventricular functional recovery.HypothesisWe hypothesized that segmental circumferential strain with displacement encoding with stimulated echoes (DENSE) would be a stronger predictor of infarct transmurality than feature‐tracking strain, and noninferior to extracellular volume fraction (ECV).Study TypeProspective.PopulationFifty participants (mean ± SD, 59 ± 9 years, 40 [80%] male) underwent cardiac MRI on day 1 post‐STEMI.Field‐Strength/Sequences1.5T/cine, DENSE, T1 mapping, ECV, LGE.AssessmentTwo observers assessed segmental percentage LGE extent, presence of microvascular obstruction (MVO), circumferential and radial strain with DENSE and feature‐tracking, T1 relaxation times, and ECV.Statistical TestsNormality was tested using the Shapiro–Wilk test. Skewed distributions were analyzed utilizing Mann–Whitney or Kruskal–Wallis tests and normal distributed data using independent t‐tests. Diagnostic cutoff values were identified using the Youden index. The difference in area under the curve was compared using the z‐statistic.ResultsSegmental circumferential strain with DENSE was associated with the extent of infarction ≥50% (AUC [95% CI], cutoff value = 0.9 [0.8, 0.9], −10%) similar to ECV (AUC = 0.8 [0.8, 0.9], 37%) (P = 0.117) and superior to feature‐tracking circumferential strain (AUC = 0.7[0.7, 0.8], −19%) (P < 0.05). For the detection of segmental infarction ≥75%, circumferential strain with DENSE (AUC = 0.9 [0.8, 0.9], −10%) was noninferior to ECV (AUC = 0.8 [0.7, 0.9], 42%) (P = 0.132) and superior to feature‐tracking (AUC = 0.7 [0.7, 0.8], −13%) (P < 0.05). For MVO detection, circumferential strain with DENSE (AUC = 0.8 [0.8, 0.9], −12%) was superior to ECV (AUC = 0.8 [0.7, 0.8] 34%) (P < 0.05) and feature‐tracking (AUC = 0.7 [0.6, 0.7] −21%) (P < 0.05).Data ConclusionCircumferential strain with DENSE is a functional measure of infarct severity and may remove the need for gadolinium contrast agents in some circumstances.Level of Evidence2Technical Efficacy Stage5 J. MAGN. RESON. IMAGING 2020;52:1722–1731.

Background: Cut off values for change in left ventricular end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) by cardiovascular magnetic resonance following ST-segment–elevation myocardial infarction have recently been proposed and 4 patterns of LV remodeling were described. We aimed to assess their long-term prognostic significance. Methods: A prospective cohort of unselected patients with ST-segment–elevation myocardial infarction with paired acute and 6-month cardiovascular magnetic resonance, with the 5-year composite end point of all-cause death and hospitalization for heart failure was included. The prognosis of the following groups (group 1: reverse LV remodeling [≥12% decrease in LVESV]; group 2: no LV remodeling [changes in LVEDV and LVESV <12%]; group 3: adverse LV remodeling with compensation [≥12% increase in LVEDV only]; and group 4: adverse LV remodeling [≥12% increase in both LVESV and LVEDV]) was compared. Results: Two hundred eighty-five patients were included with a median follow-up was 5.8 years. The composite end point occurred in 9.5% in group 1, 12.3% in group 2, 7.1% in group 3, and 24.2% in group 4. Group 4 had significantly higher cumulative event rates of the composite end point (log-rank test, P =0.03) with the other 3 groups showing similar cumulative event rates (log-rank test, P =0.51). Cox proportional hazard for group 2 (hazard ratio, 1.3 [95% CI, 0.6–3.1], P =0.53) and group 3 (hazard ratio, 0.6 [95% CI, 0.2–2.3], P =0.49) were not significantly different but was significantly higher in group 4 (hazard ratio, 3.0 [95% CI, 1.2–7.1], P =0.015) when compared with group 1. Conclusions: Patients with ST-segment–elevation myocardial infarction developing adverse LV remodeling at 6 months, defined as ≥12% increase in both LVESV and LVEDV by cardiovascular magnetic resonance, was associated with worse long-term clinical outcomes than those with adverse LV remodeling with compensation, reverse LV remodeling, and no LV remodeling, with the latter 3 groups having similar outcomes in a cohort of stable reperfused patients with ST-segment–elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02072850.

Background Impaired microcirculatory reperfusion worsens prognosis following acute ST‐segment–elevation myocardial infarction. In the T‐TIME (A Trial of Low‐Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low‐dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results A prespecified physiology substudy of the T‐TIME trial. From 2016 to 2017, patients with ST‐segment–elevation myocardial infarction ≤6 hours from symptom onset were randomized in a double‐blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2–4, and ≥4 hours) were prespecified. One hundred forty‐four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0–55.0), coronary flow reserve(1.4 [1.1–2.0]), and resistive reserve ratio (1.7 [1.3–2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance. Conclusions In ST‐segment–elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

Introduction There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia in GZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control. Methods We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ). Results 104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the target GZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve <2.0 in the target GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months. Conclusions Non-invasive evidence of major ischaemia is uncommon in patients with GZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months. Trial registration number NCT02425969.

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) (c) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.