Authors' objectives: The CaRi-Heart® device estimates risk of 8-year cardiac death, using a prognostic model, which includes perivascular fat attenuation index, atherosclerotic plaque burden and clinical risk factors. To provide an Early Value Assessment of the potential of CaRi-Heart Risk to be an effective and cost-effective adjunctive investigation for assessment of cardiac risk, in people with stable chest pain/suspected coronary artery disease, undergoing computed tomography coronary angiography. This assessment includes conceptual modelling which explores the structure and evidence about parameters required for model development, but not development of a full executable cost-effectiveness model. Coronary artery disease (CAD) and acute myocardial infarction (AMI) are a significant health burden in the UK, with ischaemic heart disease being the leading cause of death in males. Guidelines from the National Institute for Health and Care Excellence (NICE) and the European Society of Cardiology (ESC) recommend computed tomography coronary angiography (CTCA) for the investigation of CAD in people with stable chest pain. CTCA provides a visualisation of the coronary arteries, which is used to identify plaques, to quantify the extent of any stenosis of the coronary arteries and the length and location of the affected area, and to quantify the extent of coronary artery calcification. Information provided by CTCA is structural rather than functional. Acute coronary events can arise from unstable, but anatomically non-significant, atherosclerotic plaques. The vascular inflammatory response is a modulator of atherogenesis and can be a factor in plaque rupture, leading to acute coronary events. CaRi-Heart® is a cloud-based CE-marked medical device (Caristo Diagnostics Ltd, Oxford, UK) that analyses images from CTCA scans to provide information about inflammation in the coronary arteries. The CaRi-Heart device uses this information to generate a perivascular fat attenuation index (FAI) score. It then estimates individual patient risk of 8-year cardiac death with a prognostic model, which includes the perivascular FAI score, as well as atherosclerotic plaque burden and clinical risk factors. This Early Value Assessment (EVA) considers whether CaRi-Heart Risk has potential to provide an effective, safe and cost-effective adjunctive investigation for assessment of cardiac risk, in people with stable chest pain/suspected CAD, who are undergoing CTCA. This assessment does not include the development of an executable cost-effectiveness model but does include conceptual modelling which explores the structure and evidence about parameters required for model development. A series of research questions were defined that could inform both a full assessment of the clinical and cost effectiveness of using CaRi-Heart, as an adjunctive investigation for assessment of cardiac risk, in people with stable chest pain/suspected CAD, who are undergoing CTCA and consideration of the potential of this technology to be cost-effective: What is the prognostic performance of CaRi-Heart, in people with stable chest pain, who are undergoing CTCA, where: the dependent variable is cardiac death? the dependent variable is a major adverse cardiovascular event (MACE)? What is the prevalence of ‘low’, ‘medium’ and ‘high’ CaRi-Heart Risk in people with no evidence of CAD, people with evidence of non-obstructive CAD and people with evidence of obstructive CAD, based on currently available CTCA imaging? What are the clinical effects of using CaRi-Heart to assess cardiac risk? How does CaRi-Heart Risk affect treatment decisions and patient adherence in people with no evidence of CAD, people with evidence of non-obstructive CAD and people with evidence of obstructive CAD, based on currently available CTCA imaging? What are the clinical effects of any changes to treatment, based on CaRi-Heart Risk, in people with no evidence of CAD, people with evidence of non-obstructive CAD and people with evidence of obstructive CAD, based on currently available CTCA imaging? What are the costs, from a UK NHS and Personal Social Services (PSS) perspective, using CaRi-Heart, as an adjunctive investigation for assessment of cardiac risk, in people with stable chest pain, who are undergoing CTCA? How might a conceptual model be specified in terms of structure and evidence required for parameterisation in order to estimate the cost-effectiveness of CaRi-Heart in people with stable chest pain, who are undergoing CTCA?

Authors' results and conclusions: The only included study indicated that CaRi-Heart Risk may be predictive of 8 years cardiac death. The hazard ratio, per unit increase in CaRi-Heart Risk, adjusted for smoking, hypercholesterolaemia, hypertension, diabetes mellitus, Duke index, presence of high-risk plaque features and epicardial adipose tissue volume, was 1.04 (95% confidence interval 1.03 to 1.06) in the model validation cohort. Based on Prediction model Risk Of Bias ASsessment Tool, this study was rated as having high risk of bias and high concerns regarding its applicability to the decision problem specified for this Early Value Assessment. We did not identify any studies that reported information about the clinical effects or costs of using CaRi-Heart to assess cardiac risk. Exploratory searches, conducted to inform the conceptual cost-effectiveness modelling, indicated that there is a deficiency with respect to evidence about the effects of changing existing treatments or introducing new treatments, based on assessment of cardiac risk (by any method), or on measures of vascular inflammation (e.g. fat attenuation index). A de novo conceptual decision-analytic model that could be used to inform an early assessment of the cost effectiveness of CaRi-Heart is described. A combination of a short-term diagnostic model component and a long-term model component that evaluates the downstream consequences is anticipated to capture the diagnosis and the progression of coronary artery disease. The evidence about the clinical utility of CaRi-Heart Risk is underdeveloped and has considerable limitations, both in terms of risk of bias and applicability to United Kingdom clinical practice. There is some evidence that CaRi-Heart Risk may be predictive of 8-year risk of cardiac death, for patients undergoing computed tomography coronary angiography for suspected coronary artery disease. However, whether and to what extent CaRi-Heart represents an improvement relative to current standard of care remains uncertain. The evaluation of the CaRi-Heart device is ongoing and currently available data are insufficient to fully inform the cost-effectiveness modelling. Rapid review The rapid review identified one relevant model development and validation study, which included a total of 3912 patients who were undergoing clinically indicated CTCA for the evaluation of stable coronary disease. The training/development (USA) cohort comprised 2040 patients, with a median (range) follow-up duration of 53.8 (4–105) months; a total of 85 deaths were reported during follow-up, of which 48 were cardiac. The validation (Germany) cohort comprised 1872 patients, with a median (range) follow-up duration of 72 (51–109) months; there were a total of 114 deaths during follow-up, of which 26 were confirmed cardiac deaths and 16 were deaths of unknown cause. Based on Prediction model Risk Of Bias ASsessment Tool (PROBAST), this study was rated as having high risk of bias and high concerns regarding its applicability to the decision problem specified for this EVA. Importantly, there has been no external validation of the CaRi-Heart Risk model, as the reported validation data set was used in a previous study to develop methods and thresholds for the main imaging predictors (FAI scores). With respect to applicability, the CaRi-Heart study evaluated CaRi-Heart Risk for the prediction of 8-year cardiac death; it did not consider prediction of cardiac risk, as specified in the scope for this EVA (i.e. including risk of non-fatal adverse cardiovascular events). In addition, it is unclear whether the clinical comparator model can be considered representative of standard of care in the UK NHS. The included study provided information relevant to research question 1: ‘What is the prognostic performance of CaRi-Heart, in people with stable chest pain, who are undergoing CTCA where: (1) the dependent variable is cardiac death? (2) the dependent variable is MACE?’ The hazard ratio (HR) for 8-year cardiac death, per unit increase in CaRi-Heart Risk, adjusted for ‘traditional risk factors’ (smoking, hypercholesterolaemia, hypertension, diabetes mellitus, Duke index, presence of high-risk plaque features and epicardial adipose tissue volume), was 1.05 [95% confidence interval (CI) 1.03 to 1.06] in the training/development cohort and 1.04 (95% CI 1.03 to 1.06) in the validation cohort. With respect to the subgroups of clinical interest, the predictive value of the CaRi-Heart Risk model was consistent across patients with and without obstructive CAD. In addition, the results of the included study indicated that the CaRi-Heart Risk model showed improved risk discrimination, when compared to a baseline clinical risk model, which included age, sex, hypertension, hypercholesterolaemia, diabetes mellitus and smoking (Δ c-statistic 0.149, p 

Authors' methods: Twenty-four databases, including MEDLINE, MEDLINE In-Process and EMBASE, were searched from inception to October 2022. Review methods followed published guidelines. Study quality was assessed using Prediction model Risk Of Bias ASsessment Tool. Results were summarised by research question: prognostic performance; prevalence of risk categories; clinical effects; costs of CaRi-Heart. Exploratory searches were conducted to inform conceptual cost-effectiveness modelling. The rapid review methods and pragmatic additional searches used to inform this Early Value Assessment mean that, although areas of potential uncertainty have been described, we cannot definitively state where there are evidence gaps. Questions 1–4 were addressed using a rapid review process. Twenty-four databases were searched from inception to October 2022, using a variety of databases including MEDLINE, EMBASE, Cochrane, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Kleijnen Systematic Reviews Ltd (KSR) Evidence and Epistemonikos. One reviewer screened titles and abstracts of all reports identified by the searches, and a minimum of 20% were independently screened by a second reviewer. Full copies of all studies deemed potentially relevant, by either reviewer, were obtained and both reviewers independently assessed these for inclusion; any disagreements were resolved by consensus or discussion with a third reviewer. Data were extracted by one reviewer and checked by a second reviewer; any disagreements were resolved by consensus or discussion with a third reviewer. Study quality was assessed using appropriate risk-of-bias tools. Results were summarised by research question: prognostic performance; prevalence of risk categories; clinical effects; costs of CaRi-Heart. In addition to the rapid review, evidence that might be required to inform parameterisation of a future cost-effectiveness model was explored, as part of the conceptual modelling process, using a pragmatic, iterative searching approach; model parameterisation questions, other than costs, were not included in the rapid review.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR135672

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/WYGC4096

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/WYGC4096

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk