ECHO-MPS, a dual modality strategy of cardiac imaging to identify myocardial ischemia

Purpose: We aimed to evaluate an approach with resting echocardiography (TTE) and stress myocardial perfusion scintigraphy (MPS) compared to standard MPS in patients with stable angina and normal left ventricle (LV). We hypothesized that normal LV on TTE may allow for the elimination of rest MPS without compromising accuracy and offering an efficient diagnostic pathway with reduced radiation exposure. Methods: In a prospective, non-randomized study TTE was performed prior to MPS in patients (pts) referred for assessment of coronary artery disease (CAD). In pts with normal LV assessment was performed using the hybrid and the standard approach. TTE and MPS were interpreted by two TTE readers (ER1-2) and two MPS readers (NR1-2). ECHO-MPS was compared with standard MPS for diagnostic accuracy. Results: 103 patients, mean age 61 ± 12 year, (63 M, 40 W) were recruited. Standard MPS were normal in 75 patients and abnormal in 28 patients, with the hybrid approach 79 studies were reported as normal and 24 studies as abnormal. Kappa values were 0.580, (p < 0.001) for large, 0.394, (p < 0.001) for medium, and 0.298 (p = 0.002) for small defects. With standard MPS as a reference, sensitivity for detection of perfusion defects by ECHO-MPS was 75% (95% CI 0.67–0.83) [NR2] and 78% (95% CI 0.70–0.86)[NR1]. Specificity was 95% (95% CI 0.90–0.99) [NR2] and 95% (CI 95%CI 0.90–0.99) [NR1]. Conclusions: ECHO-MPS protocol provides similar diagnostic accuracy as standard stress-rest MPS. In patients with normal systolic LV function in TTE, performing only stress MPS provides similar information as standard rest and stress MPS

Exploring cardiovascular involvement in IgG4-related disease: a case series approach with cardiovascular magnetic resonance

Background: IgG4-related disease (IgG4-RD) is a relapsing–remitting, fibroinflammatory, multisystem disorder. Cardiovascular involvement from IgG4-RD has not been systematically characterised. In this study, we sought to evaluate consecutive patients with IgG4-RD using a detailed multiparametric cardiovascular magnetic resonance (CMR) imaging protocol. Methods: We prospectively enrolled 11 patients with histology-confirmed IgG4-RD; with active disease at time of scan. We undertook a detailed multiparametric CMR imaging protocol at 1.5T including cine imaging, native T1 and T2 mapping, stress perfusion imaging with inline quantitation of myocardial blood flow and late gadolinium enhancement (LGE) imaging. Results: All patients exhibited at least one abnormality on CMR imaging. Abnormal elevation of global or segmental left ventricular myocardial T1 and T2 values was present in four patients, suggesting myocardial oedema or inflammation. Abnormal LGE, suggesting myocardial scar fibrosis, was present in nine patients, with eight displaying a non-ischaemic pattern, and one showing an ischaemic pattern. Four patients fulfilled both Lake Louise Criteria for active myocardial inflammation, while a further six fulfilled one criterion. Myocardial perfusion reserve was normal in all evaluable patients. Ten patients had normal ventricular volumes, mass and systolic function. In addition, thoracic aortitis was identified in three patients who underwent 18F-flourodeoxyglucose PET/CT imaging, with resolution following anti-B-cell treatment. Conclusions: In this cohort of patients with histology-confirmed IgG4-RD, multiparametric CMR revealed no changes in gross cardiac structure and function, but frequent myocardial tissue abnormalities. These data suggest a plausible pathophysiological link between IgG4-RD and cardiovascular involvement

Long-term outcomes after stress echocardiography in real world practice: five-year follow-up of the UK Evarest study

Aims: Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real-world practice across a healthcare system has not been previously reported. Methods and results: Five thousand five hundred and three patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in the analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions, and relevant cardiovascular diagnoses, based on Kaplan–Meier analysis and Cox proportional hazard ratios (HRs). Median follow-up was 829 days (interquartile range 224–1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction [HR 2.71, 95% confidence interval (CI) 1.73–4.24, P < 0.001] and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41–2.93, P < 0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free ‘warranty period’ of at least 5 years in patients with no prior history of coronary artery disease and 4 years for those with disease. Conclusion: In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorizes risk of future events over the next 5 years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period

Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data

Background Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker—the perivascular fat attenuation index (FAI)—captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown. Methods In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries—the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features. Findings Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17–89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19–87]). Median follow-up was 72 months (range 51–109) in the derivation cohort and 54 months (range 4–105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33–3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50–2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35–24·40; p<0·0001 for cardiac mortality; 2·55, 1·65–3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90–10·88; p<0·0001 for cardiac mortality; 3·69, 2·26–6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality. Interpretation The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥–70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients

Changes in coronary disease management decisions in real-world practice between 2015 and 2023: insights from the EVAREST/BSE-NSTEP observational study

Aims: To assess the real-world impact of updated clinical guidelines and literature on the management of patients undergoing stress echocardiography for the assessment of inducible ischaemia across a national health service. Methods and results: A total of 13 819 patients from 32 UK hospitals, referred for stress echocardiography between 2015 and 2023, were analysed across two phases: phase 1 (2015–2020) and phase 2 (2020–2023). Follow-up data for 1 year was available for 4920 participants through NHS Digital. Patients in phase 2 were younger and presented with a higher cardiovascular risk profile, although sex distribution remained similar across phases. There was an observed reduction in invasive angiography referrals within 1 year following a positive stress echocardiogram (P < 0.01), which appeared to be attributed to changes in the management of patients with moderate ischaemia (3–4 segments; P < 0.01). For those who did receive invasive assessment, there were no changes in intervention rate (P = 0.27), regardless of ischaemic burden. This trend was most evident in centres performing a higher volume of stress echocardiograms. Conclusion: Coronary disease management pathways have changed within the UK and fewer patients with moderate ischaemia are undergoing invasive coronary angiography. However, coronary intervention rates are unchanged, suggesting that stress echocardiography is being used to improve patient selection for invasive procedures while minimizing unnecessary referrals. Future work will assess if this reduction in angiography referrals is maintained long term, and if there are any effects on patient outcomes

Cost-effectiveness of a novel AI technology to quantify coronary inflammation and cardiovascular risk in patients undergoing routine Coronary Computed Tomography Angiography.

AIMS: Coronary Computed Tomography Angiography (CCTA) is a first line investigation for chest pain in patients with suspected obstructive coronary artery disease (CAD). However, many acute cardiac events occur in the absence of obstructive CAD. We assessed the lifetime cost-effectiveness of integrating a novel artificial intelligence-enhanced image analysis algorithm (AI-Risk) that stratifies the risk of cardiac events by quantifying coronary inflammation, combined with the extent of coronary artery plaque and clinical risk factors, by analysing images from routine CCTA. METHODS AND RESULTS: A hybrid decision-tree with population cohort Markov model was developed from 3,393 consecutive patients who underwent routine CCTA for suspected obstructive CAD and followed up for major adverse cardiac events over a median(IQR) of 7.7(6.4-9.1) years. In a prospective real-world evaluation survey of 744 consecutive patients undergoing CCTA for chest pain investigation, the availability of AI-Risk assessment led to treatment initiation or intensification in 45% of patients. In a further prospective study of 1,214 consecutive patients with extensive guideline recommended cardiovascular risk profiling, AI-Risk stratification led to treatment initiation or intensification in 39% of patients beyond the current clinical guideline recommendations. Treatment guided by AI-Risk modelled over a lifetime horizon could lead to fewer cardiac events (relative reductions of 4%, 4%, 11%, and 12% for myocardial infarction, ischaemic stroke, heart failure and cardiac death, respectively). Implementing AI-Risk classification in routine interpretation of CCTA is highly likely to be cost-effective (Incremental cost-effectiveness ratio £1,371-3,244), both in scenarios of current guideline compliance or when applied only to patients without obstructive CAD. CONCLUSIONS: Compared with standard care, the addition of AI-Risk assessment in routine CCTA interpretation is cost effective, by refining risk guided medical management

Coronary Atherosclerotic Plaque Activity and Future Coronary Events

This study was funded by a Wellcome Trust Senior Investigator Award (WT103782AIA). Image analysis was supported by National Institutes for Health (R34HL161195 and 1R01HL135557). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Wellcome Trust or the National Institutes of Health. The British Heart Foundation supports DEN (CH/09/002, RG/16/10/32375, RE/18/5/34216), MRD (FS/SCRF/21/32010), NLM (CH/F/21/90010, RG/20/10/34966, RE/18/5/34216) AJM (AA/18/3/34220) and MCW (FS/ICRF/20/26002) and DD (FS/RTF/20/30009, NH/19/1/34595, PG/18/35/33786, PG/15/88/31780, PG/17/64/33205). MRD is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). PJS is supported by outstanding investigator award National Institutes for Health (R35HL161195). JK is supported by the National Science Centre 2021/41/B/NZ5/02630. EvB is supported by SINAPSE (www.sinapse.ac.uk). AB is supported by a Clinical Research Training Fellowships (MR/V007254/1). DD is supported by Chest Heart and Stroke Scotland (19/53), Tenovus Scotland (G.18.01), and Friends of Anchor and Grampian NHS-Endowments. The Edinburgh Clinical Research Facilities, Edinburgh Imaging facility and Edinburgh Clinical Trials Unit are supported by the National Health Service Research Scotland through National Health Service Lothian Health Board. The Leeds Clinical Research Facilities are supported by the UK National Institute for Health Research (NIHR) via its Clinical Research Facility programme. The work at Cedars-Sinai Medical Center (the Los Angeles site) was supported in part by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. The Chief Investigator and Edinburgh Clinical Trials Unit had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Peer reviewedPostprin

Benefits outweigh the risks: a consensus statement on the risks of physical activity for people living with long-term conditions

Introduction The benefits of physical activity for people living with long-term conditions (LTCs) are well established. However, the risks of physical activity are less well documented. The fear of exacerbating symptoms and causing adverse events is a persuasive barrier to physical activity in this population. This work aimed to agree clear statements for use by healthcare professionals about medical risks of physical activity for people living with LTCs through expert consensus. These statements addressed the following questions: (1) Is increasing physical activity safe for people living with one or more LTC? (2) Are the symptoms and clinical syndromes associated with common LTCs aggravated in the short or long term by increasing physical activity levels? (3) What specific risks should healthcare professionals consider when advising symptomatic people with one or more LTCs to increase their physical activity levels? Methods Statements were developed in a multistage process, guided by the Appraisal of Guidelines for Research and Evaluation tool. A patient and clinician involvement process, a rapid literature review and a steering group workshop informed the development of draft symptom and syndrome-based statements. We then tested and refined the draft statements and supporting evidence using a three-stage modified online Delphi study, incorporating a multidisciplinary expert panel with a broad range of clinical specialties. Results Twenty-eight experts completed the Delphi process. All statements achieved consensus with a final agreement between 88.5%–96.5%. Five ‘impact statements’ conclude that (1) for people living with LTCs, the benefits of physical activity far outweigh the risks, (2) despite the risks being very low, perceived risk is high, (3) person-centred conversations are essential for addressing perceived risk, (4) everybody has their own starting point and (5) people should stop and seek medical attention if they experience a dramatic increase in symptoms. In addition, eight symptom/syndrome-based statements discuss specific risks for musculoskeletal pain, fatigue, shortness of breath, cardiac chest pain, palpitations, dysglycaemia, cognitive impairment and falls and frailty. Conclusion Clear, consistent messaging on risk across healthcare will improve people living with LTCs confidence to be physically active. Addressing the fear of adverse events on an individual level will help healthcare professionals affect meaningful behavioural change in day-to-day practice. Evidence does not support routine preparticipation medical clearance for people with stable LTCs if they build up gradually from their current level. The need for medical guidance, as opposed to clearance, should be determined by individuals with specific concerns about active symptoms. As part of a system-wide approach, consistent messaging from healthcare professionals around risk will also help reduce cross-sector barriers to engagement for this population.Output Status: Forthcoming/Available Onli

Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study

Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. Methods: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4–5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4–9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. Findings: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9–63·9], p<0·001) or MACE (12·6 [8·5–18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17–8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93–5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. Interpretation: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators