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Aims To determine population-related and technical sources of variation in cardiac magnetic resonance (CMR) reference ranges for left ventricular (LV) quantification through a formal systematic review and meta-analysis. Methods and results This study is registered with the International Prospective Register of Systematic Reviews (CRD42019147161). Relevant studies were identified through electronic searches and assessed by two independent reviewers based on predefined criteria. Fifteen studies comprising 2132 women and 1890 men aged 20–91 years are included in the analysis. Pooled LV reference ranges calculated using random effects meta-analysis with inverse variance weighting revealed significant differences by age, sex, and ethnicity. Men had larger LV volumes and higher LV mass than women [LV end-diastolic volume (mean difference = 6.1 mL/m2, P-value = 0.014), LV end-systolic volume (MD = 4 mL/m2, P-value = 0.033), LV mass (mean difference = 12 g/m2, P-value = 7.8 × 10−9)]. Younger individuals had larger LV end-diastolic volumes than older ages (20–40 years vs. ≥65 years: women MD = 14.0 mL/m2, men MD = 14.7 mL/m2). East Asians (Chinese, Korean, Singaporean-Chinese, n = 514) had lower LV mass than Caucasians (women: MD = 6.4 g/m2, P-value = 0.016; men: MD = 9.8 g/m2, P-value = 6.7 × 10−5). Between-study heterogeneity was high for all LV parameters despite stratification by population-related factors. Sensitivity analyses identified differences in contouring methodology, magnet strength, and post-processing software as potential sources of heterogeneity. Conclusion There is significant variation between CMR normal reference ranges due to multiple population-related and technical factors. Whilst there is need for population-stratified reference ranges, limited sample sizes and technical heterogeneity precludes derivation of meaningful unified ranges from existing reports. Wider representation of different populations and standardization of image analysis is urgently needed to establish such reference distributions., Graphical Abstract

Background: Non-invasive Cardiovascular imaging (NICI), including cardiovascular magnetic resonance (CMR) imaging provides important information to guide the management of patients with cardiovascular conditions. Current rates of NICI use and potential policy determinants in the United States of America (US) and England remain unexplored.Methods: We compared NICI activity in the US (Medicare fee-for-service, 2011–2015) and England (National Health Service, 2012–2016). We reviewed recommendations related to CMR from Clinical Practice Guidelines, Appropriate Use Criteria (AUC), and Choosing Wisely. We then categorized recommendations according to whether CMR was the only recommended NICI technique (substitutable indications). Reimbursement policies in both settings were systematically collated and reviewed using publicly available information.Results: The 2015 rate of NICI activity in the US was 3.1 times higher than in England (31,055 vs. 9,916 per 100,000 beneficiaries). The proportion of CMR of all NICI was small in both jurisdictions, but nuclear cardiac imaging was more frequent in the US in absolute and relative terms. American and European CPGs were similar, both in terms of number of recommendations and proportions of indications where CMR was not the only recommended NICI technique (substitutable indications). Reimbursement schemes for NICI activity differed for physicians and hospitals between the two settings.Conclusions: Fee-for-service physician compensation in the US for NICI may contribute to higher NICI activity compared to England where physicians are salaried. Reimbursement arrangements for the performance of the test may contribute to the higher proportion of nuclear cardiac imaging out of the total NICI activity. Differences in CPG recommendations appear not to explain the variation in NICI activity between the US and England.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AK has been funded by the Egyptian cultural centre and educational bureau of the Egyptian embassy in London and the Ministry of higher education in Egypt. SEP acknowledges support from the “SmartHeart” EPSRC programme grant (www.nihr.ac.uk; EP/P001009/1) and the London Medical Imaging and AI Centre for Value-Based Healthcare. This new centre is one of the UK Centres supported by a £50m investment from the Data to Early Diagnosis and Precision Medicine strand of the government’s Industrial Strategy Challenge Fund, managed and delivered by UK Research and Innovation (UKRI). SEP acknowledges support from the CAP-AI programme, London’s first AI enabling programme focused on stimulating growth in the capital’s AI Sector. CAP-AI is led by Capital Enterprise in partnership with Barts Health NHS Trust and Digital Catapult and is funded by the European Regional Development Fund and Barts Charity. SEP also acts as a paid consultant to Circle Cardiovascular Imaging Inc., Calgary, Canada and Servier onbehalf Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS Trust, West Smithfield, London, UK Background Manual contouring of cardiovascular magnetic resonance (CMR) cine images remains common practice and the reference standard for left ventricular (LV) volumes and mass evaluation. However, it is time-consuming and machine learning (ML) may significantly reduce the time required for contouring. Accurate LV contours are the basis for reliable LV strain analysis using tissue tracking. Purpose To assess the impact of a ML contouring tool alone versus expert adjusted contours on LV strain. Methods We retrospectively selected 402 CMR studies with diagnoses of myocardial infarction (n = 108), myocarditis (n = 130) and healthy controls (n = 164) from the Barts BioResource between January 2015 to June 2018. CMR examinations were obtained using 1.5T and 3T scanners (Siemens Healthineers, Germany). We excluded 32 cases due to phase inconsistency between short (SAX) and long axes (LAX) cine images or suboptimal cine image quality. For the remaining 370 cases, steady state free precession cine images for LAX and SAX were analysed by the ML contouring tool (using CVI42 research prototype software 5.11). Manual expert adjustment for the contours was done for each case if considered suboptimal for strain analysis in the reference end-diastolic phase. Strain results from ML and expert adjusted ML methods were compared for strain agreement. Times taken by these methods were recorded and compared against the time taken for standard manual contouring. Results SAX and LAX derived strains by ML and expert adjusted ML methods showed good agreement by Bland-Altman analysis (Figure 1) with excellent coefficient of concordance using Kendall W which is 0.98 for global SAX, radial and circumferential strains (mean difference(MD) = -1.7% (lower and upper limits of agreement (UL,LL) -6.6,3.2), MD = 0.5% (-1.0,2.1)) and is 0.95 for global LAX derived strain (radial and longitudinal, MD = 0.7% (UL,LL -8.7 ,7.4),MD= 0.2% (-1.9,2.5), respectively). Time taken for adjustment of ML contours was significantly shorter than manual contouring (1.35 minutes vs 8.0 minutes, around 590% time saving in ML adjusted method). Conclusions ML contouring compared to expert manual adjustment has a clinically reasonable agreement when used for measuring LV strain. Also, using the ML tool with expert adjustment shows significant time saving for analysis and reporting time compared to entirely manual analysis, favouring its application in routine clinical practice. Abstract Figure.

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