A history of cardiovascular magnetic resonance imaging in clinical practice and population science

medRxiv

We used expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) to conduct genome-wide Mendelian randomization (MR) using 27,799 cases of heart failure (HF) with reduced ejection fraction (HFrEF), 27,579 cases of HF with preserved ejection fraction (HFpEF), and 367,267 control individuals from the Million Veteran Program (MVP). We identified 70 HFrEF and 10 HFpEF gene-hits, of which 58 are novel. In 14 known loci for unclassified HF, we identified HFrEF as the subtype responsible for the signal. HFrEF hits ZBTB17, MTSS1, PDLIM5, and MLIP and novel HFpEF hits NFATC2IP, and PABPC4 showed robustness to MR assumptions, support from orthogonal sources, compelling evidence on mechanism of action needed for therapeutic efficacy, and no evidence of an unacceptable safety profile. We strengthen the value of pathways such as ubiquitin-proteasome system, small ubiquitin-related modifier pathway, inflammation, and mitochondrial metabolism as potential therapeutic targets for HF management. We identified IL6R, ADM, and EDNRA as suggestive hits for HFrEF and LPA for HFrEF and HFpEF, which enhances the odds of success for existing cardiovascular investigational drugs targeting. These findings confirm the unique value of human genetic studies in HFrEF and HFpEF for discovery of novel targets and generation of therapeutic target profiles needed to initiate new validation programs in HFrEF and HFpEF preclinical models.

International Journal of Epidemiology

Data from a single study are rarely sufficient to comprehensively understand a phenomenon of interest or to build predictive models with statistical power. Meta-analyses, including aggregated data for several cohort studies, can be carried out to synthesize published results, but the use of harmonized individual-level data from different studies is preferable to reach the maximal comparability across the studies. A significant barrier to the co-analysis approach is finding relevant studies and accessing their data.Such barriers have, amongst others, led to designing the FAIR (Findable, Accessible, Interoperable and Reusable) principles, which have been recognized internationally. 1 Currently, it is still difficult to obtain a comprehensive overview of available data from existing observational studies on cardiovascular diseases. Because there is no requirement to register studies other than clinical trials, information on …

Journal of Cardiovascular Magnetic Resonance

Background: Left ventricular (LV) mass is a known prognostic cardiovascular biomarker with established genetic underpinnings, and is a particularly important phenotype in the context of heart muscle diseases. Physical activity holds interest as a risk factor as in general, it is protective against cardiovascular disease, however, in certain circumstances it can lead to deleterious remodelling. This gene-lifestyle interaction study examines whether physical activity attenuates the effect of genetic variants known to be associated with LV mass.Methods: Genotype data (number of risk alleles) for 12 variants known to be associated with LV mass were retrieved for all participants in the UK Biobank. Of these, 42,309 had paired CMR and physical activity data. LV mass was indexed to body surface area. Physical activity levels in metabolic equivalent of task (MET)-minutes were determined from self-reported questionnaire data …

Journal of Cardiovascular Magnetic Resonance

Background: Hypertrophic cardiomyopathy (HCM) is a relatively common cardiomyopathy (affecting approximately 1 in 500 individuals) with a typically autosomal dominant inheritance. Preclinical HCM is defined as gene positive, left ventricular hypertrophy negative cases (G+ LVH-). It is crucial to identify gene carriers before the onset of overt left ventricular hypertrophy in preclinical phase to initiate early interventions and potentially halt the progression of the disease. Utilizing cardiovascular magnetic resonance (CMR) can be invaluable for early disease detection, as it can reveal specific imaging features indicative of preclinical HCM, thereby guiding timely medical responses and possibly preventing severe outcomes. Here, we aimed to investigate the value of integrating standard CMR measures and radiomics features in discriminating subclinical HCM using machine learning methods.Methods: We enrolled 51 …

arXiv preprint arXiv:2403.19508

The progress in deep learning solutions for disease diagnosis and prognosis based on cardiac magnetic resonance imaging is hindered by highly imbalanced and biased training data. To address this issue, we propose a method to alleviate imbalances inherent in datasets through the generation of synthetic data based on sensitive attributes such as sex, age, body mass index, and health condition. We adopt ControlNet based on a denoising diffusion probabilistic model to condition on text assembled from patient metadata and cardiac geometry derived from segmentation masks using a large-cohort study, specifically, the UK Biobank. We assess our method by evaluating the realism of the generated images using established quantitative metrics. Furthermore, we conduct a downstream classification task aimed at debiasing a classifier by rectifying imbalances within underrepresented groups through synthetically generated samples. Our experiments demonstrate the effectiveness of the proposed approach in mitigating dataset imbalances, such as the scarcity of younger patients or individuals with normal BMI level suffering from heart failure. This work represents a major step towards the adoption of synthetic data for the development of fair and generalizable models for medical classification tasks. Notably, we conduct all our experiments using a single, consumer-level GPU to highlight the feasibility of our approach within resource-constrained environments. Our code is available at https://github.com/faildeny/debiasing-cardiac-mri.

Rationale Chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction (HFpEF) have both shown increased prevalence, morbidity and mortality over the past decades. Previous studies have found impaired left ventricular filling in COPD and emphysema. In addition, pulmonary vascular changes have been linked to the impaired filling suggesting an upstream mechanism that remains unclear. 4D-flow MRI (3D+ time) is a reliable and reproducible imaging technique that gives comprehensive, time-resolved hemodynamic assessment. We aimed to use 4D-flow derived measurements to characterize the cardiopulmonary hemodynamic interactions in COPD. Methods SPIROMICS is a multicenter, longitudinal case-control study that recruited COPD cases with 20+ packyears of smoking and controls. SPIROMICS HF is adding detailed cardiac phenotyping including cardiac MRIs in up …

JACC: Cardiovascular Imaging

BackgroundThe absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care.ObjectivesThis paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date.MethodsCMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established …

European Heart Journal-Cardiovascular Imaging

Aims Clinical likelihood (CL) models are designed based on a reference of coronary stenosis in patients with suspected obstructive coronary artery disease. However, a reference standard for myocardial perfusion defects (MPDs) could be more appropriate. We aimed to investigate the ability of the 2019 European Society of Cardiology pre-test probability (ESC-PTP), the risk-factor-weighted (RF-CL) model, and coronary artery calcium score-weighted (CACS-CL) model to diagnose MPDs. Methods and results Symptomatic stable de novo chest pain patients (n = 3374) underwent coronary computed tomography angiography and subsequent myocardial perfusion imaging by single-photon emission computed tomography, positron emission tomography, or cardiac magnetic resonance. For all modalities, MPD was defined as coronary computed tomography angiography with …

Cardiovascular Imaging

Left atrial (LA) function and left ventricular (LV) myocardial fibrosis have complex bidirectional relationships via common pathways, including aberrant myocardial remodeling and LV diastolic dysfunction. 1 Although native T1 (which reflects myocardial diffuse fibrosis) and LA function have each been independently linked with cardiovascular events, no studies have investigated how these parameters in combination influence clinical outcomes. We evaluated the relationship between T1 and LA global and phasic function in the UK Biobank imaging study 2 and report the association of concurrent aberration of T1 and LA function with incident events. A total of 34,189 participants free from cardiovascular (CV) disease were included. The study is covered by the overall UK Biobank ethical approval (NHS National Research Ethics Service 21/NW/0157). T1 mapping was performed using the Shortened Modified Look …

Imaging Neuroscience

Elevated vascular disease risk associates with poorer cognitive function, but the mechanism for this link is poorly understood. A leading theory, the structural-functional model argues that vascular risk may drive adverse cardiac remodelling, which, in turn, leads to chronic cerebral hypoperfusion and subsequent brain structural damage. This model predicts that variation in heart and brain structure should associate with both greater vascular risk and lower cognitive function. This study tests that prediction in a large sample of the UK Biobank (N = 11,962). We assemble and summarise vascular risk factors, cardiac magnetic resonance radiomics, brain structural and diffusion MRI indices, and cognitive assessment. We also extract “heart-brain axes” capturing the covariation in heart and brain structure. Many heart and brain measures partially explain the vascular risk—cognitive function association, like left …

Journal of Cardiovascular Magnetic Resonance

Background: Myocardial strain using cardiac magnetic resonance (CMR) is a sensitive marker for predicting adverse outcomes in many cardiac disease states. The most promising and widely reported metric is left ventricular global longitudinal strain (LV GLS)(1, 2). Left ventricular global circumferential strain (LV GCS) and global radial strain (LV GRS) may also have prognostic value, but there are fewer studies demonstrating this (3–5). The prognostic value of myocardial strain in the general population has not been studied conclusively.Methods: Participants from the UK Biobank population imaging study were included (n~ 45,700, age 65±8 years)–see Table 1 for all baseline characteristics. CMR feature tracking (FT) derived LV GLS, GCS and GRS (see Figure 1) metrics were assessed for their prognostic value in predicting adverse outcomes (heart failure (HF), myocardial infarction (MI), stroke and death …

Journal of Cardiovascular Magnetic Resonance

Background: Patients with breast cancer (BC) have a heightened cardiovascular risk. Cardiovascular magnetic resonance (CMR) provides organ-level information about cardiovascular health and has a potential role in risk stratification. Building on our previous work in this area, we examined cardiovascular disease (CVD) associations and CMR remodelling patterns in UK Biobank participants with past BC, considering an expanded range of image-derived phenotypes.Methods: BC status was defined as record of the diagnosis prior to baseline recruitment. Comparators were participants without any record of BC. In the whole cohort, we examined associations with a range of incident CVDs, ascertained from health record linkage. CMR associations were considered in the subset of participants completing the UK Biobank Imaging Study. Imaging was with 1.5 T (Siemens Healthcare) scanners per standardised …

Population aging is one of the most important demographic transformations of our time. Increasing the “health span”—the proportion of life spent in good health—is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to …

BMC medicine

BackgroundThe NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not.MethodsWithin the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records. These participants were then covariate-matched on an extensive range of socio-demographic, lifestyle, and medical factors with 48,602 participants without record of the check. Follow-up diagnoses were ascertained from health records over an average of 9 years (SD 2 years) including hypertension, diabetes, hypercholesterolaemia, stroke …

JACC: Cardiovascular Imaging

Non-invasive techniques for tracking biological aging of the cardiovascular system Toggle navigation Login Toggle navigation Non-invasive techniques for tracking biological aging of the cardiovascular system QMRO Home William Harvey Research Institute NIHR Advanced Imaging Non-invasive techniques for tracking biological aging of the cardiovascular system QMRO Home William Harvey Research Institute NIHR Advanced Imaging Non-invasive techniques for tracking biological aging of the cardiovascular system All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects Login Most Popular ItemsStatistics by CountryMost Popular Authors Non-invasive techniques for tracking biological aging of the cardiovascular system View/Open Accepted version Embargoed until: 2099-01-01 Reason: Not Yet Published Publisher Elsevier Journal JACC: …

Journal of Cardiovascular Magnetic Resonance

Background: Left ventricular (LV) mass is a known prognostic cardiovascular biomarker with established genetic underpinnings, and is a particularly important phenotype in the context of heart muscle diseases. Physical activity holds interest as a risk factor as in general, it is protective against cardiovascular disease, however, in certain circumstances it can lead to deleterious remodelling. This gene-lifestyle interaction study examines whether physical activity attenuates the effect of genetic variants known to be associated with LV mass.Methods: Genotype data (number of risk alleles) for 12 variants known to be associated with LV mass were retrieved for all participants in the UK Biobank. Of these, 42,309 had paired CMR and physical activity data. LV mass was indexed to body surface area. Physical activity levels in metabolic equivalent of task (MET)-minutes were determined from self-reported questionnaire data …

Journal of the American College of Cardiology

BackgroundOur understanding of the specific aspects of vascular contributions to dementia remains incomplete. We aim to identify the correlates of incident dementia in a multi-ethnic cardiovascular cohort.MethodsA total of 6806 participants with follow-up data for incident dementia were included. Probable dementia diagnoses were identified using hospitalization discharge diagnoses according to the International Classification of Diseases Codes (ICD). We used Random Survival Forest analysis to identify the correlates of incident dementia from among 198 variables collected at the baseline MESA exam entailing demographic risk factors, past medical history, anthropometric measurements, laboratory markers, electrocardiogram, cardiac and aortic magnetic resonance imaging, coronary artery calcium and liver fat content. Death and stroke were considered competing risks.ResultsOver 14 years of follow-up, 326 …

Radiology

Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep …

RATIONALE Chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction (HFpEF) are leading causes of hospitalization and mortality and often overlap clinically. The heart and lungs have developmental, molecular, anatomical and physiologic linked yet are often studied separately. We provide initial completion and reproducibility measures of echocardiography and cardiopulmonary MRI measures in a large multicenter study of cardiac