Adverse cardiovascular magnetic resonance phenotypes are associated with greater likelihood of incident coronavirus disease 2019: findings from the UK Biobank.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes. AIMS: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19. METHODS: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction. RESULTS: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity. DISCUSSION: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors. CONCLUSIONS: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations

Right Ventricular Structure and Function in Elite Athletes in Relation to Pre-Participation Screening

Cardiovascular adaptations to long-term high intensity causes physiological remodelling of the Right ventricle (RV) due to frequent exposure to elevated exercise intensity. Evidence suggests dynamic exercise training serves as the primarily stimulator for the RV adaptation. This cardiac adaption might exceed the cut off limit meeting structural criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) disease. Athlete pre-participation screening is focused on detecting pathological conditions like ARVC. Current issues include: indices that differentiated ARVC patients and healthy people; the impact of different levels of dynamic training exposure on the RV structure, function in elite male athletes; insight into the RV structural and functional in those athletes meet the structural TFC (MTFC) for ARVC and those that do not (NMTFC) via utilising 12-leads Electrocardiography (ECG) and echocardiography. Study one is a systematic review and meta-analysis technique that employed a case-control design sought to determine the extent of the RV structural and functional ranges in ARVC. In second study, athletes were grouped according to their sporting discipline using the Mitchell Classification as Low Dynamic (LD), Moderate Dynamic (MD) or High Dynamic (HD) and underwent through traditional and novel echocardiography techniques with a focused and comprehensive assessment of the RV. In study 3, athletes were grouped to MTFC for ARVC and those NMTFC. Study four, retrospective study looking at the 12-lead ECG for athletes in study MTFC compared to NMTFC. The key finding form the first study was a significant differences in a range of structural and functional echocardiographic parameters between ARVC patients and healthy control participants. Patients with ARVC had larger RV outflow tract (RVOT) diameter at short-axis view (mean SD; 34 vs. 28 mm P0.01). The base to apex ε gradient in the RV septum was lower in the MD athletes compared to HD and LD due to a lower apical septal ε which significantly correlated with absolute RV chamber size. In third study, MTFC had larger absolute and scaled RVOT diameter compared to NMTFC (P ˂0.05) but these athletes did not develop a proportional increase in the RV inflow dimensions. MTFC also had lower global RV ε, peak systolic and late diastolic tissue velocity compared to NMTFC. Study four, MTFC had generally normal ECG finding compared to NMTFC. The finding have important implication for cardiovascular screening of athletes

Diagnostic Challenges in Sports Cardiology

The foundations of sports cardiology include promoting physical activity and providing a safe environment for training and competition for all athletes at all levels, from professional to recreational. To combine these two aims, reliable tools to perform preparticipation screenings are needed. Moreover, those at high risk of potentially life-threatening events should be advised to limit their training load, while others should be reassured that there is no exercise-related cardiovascular risk. We are currently witnessing the advent of new portable devices for remote and mobile heart monitoring and several new and promising biochemical markers, which can support athletes’ diagnostic processes. In this Special Issue of the Diagnostics journal entitled “Diagnostic Challenges in Sports Cardiology”, we present a series of 13 manuscripts, including eight original works, three reviews, and two case reports, which give a glimpse into the current research topics in the area of sports cardiology

The anthropometric, environmental and genetic determinants of right ventricular structure and function

BACKGROUND Measures of right ventricular (RV) structure and function have significant prognostic value. The right ventricle is currently assessed by global measures, or point surrogates, which are insensitive to regional and directional changes. We aim to create a high-resolution three-dimensional RV model to improve understanding of its structural and functional determinants. These may be particularly of interest in pulmonary hypertension (PH), a condition in which RV function and outcome are strongly linked. PURPOSE To investigate the feasibility and additional benefit of applying three-dimensional phenotyping and contemporary statistical and genetic approaches to large patient populations. METHODS Healthy subjects and incident PH patients were prospectively recruited. Using a semi-automated atlas-based segmentation algorithm, 3D models characterising RV wall position and displacement were developed, validated and compared with anthropometric, physiological and genetic influences. Statistical techniques were adapted from other high-dimensional approaches to deal with the problems of multiple testing, contiguity, sparsity and computational burden. RESULTS 1527 healthy subjects successfully completed high-resolution 3D CMR and automated segmentation. Of these, 927 subjects underwent next-generation sequencing of the sarcomeric gene titin and 947 subjects completed genotyping of common variants for genome-wide association study. 405 incident PH patients were recruited, of whom 256 completed phenotyping. 3D modelling demonstrated significant reductions in sample size compared to two-dimensional approaches. 3D analysis demonstrated that RV basal-freewall function reflects global functional changes most accurately and that a similar region in PH patients provides stronger survival prediction than all anthropometric, haemodynamic and functional markers. Vascular stiffness, titin truncating variants and common variants may also contribute to changes in RV structure and function. CONCLUSIONS High-resolution phenotyping coupled with computational analysis methods can improve insights into the determinants of RV structure and function in both healthy subjects and PH patients. Large, population-based approaches offer physiological insights relevant to clinical care in selected patient groups.Open Acces

Novel cardiovascular magnetic resonance phenotyping of the myocardium

INTRODUCTION Left ventricular (LV) microstructure is unique, composed of a winding helical pattern of myocytes and rotating aggregations of myocytes called sheetlets. Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease characterised by left ventricular hypertrophy (LVH), however the link between LVH and underlying microstructural aberration is poorly understood. In vivo cardiovascular diffusion tensor imaging (cDTI) is a novel cardiovascular MRI (CMR) technique, capable of characterising LV microstructural dynamics non-invasively. In vivo cDTI may therefore improve our understanding microstructural-functional relationships in health and disease. METHODS AND RESULTS The monopolar diffusion weighted stimulated echo acquisition mode (DW-STEAM) sequence was evaluated for in vivo cDTI acquisitions at 3Tesla, in healthy volunteers (HV), patients with hypertensive LVH, and HCM patients. Results were contextualised in relation to extensively explored technical limitations. cDTI parameters demonstrated good intra-centre reproducibility in HCM, and good inter-centre reproducibility in HV. In all subjects, cDTI was able to depict the winding helical pattern of myocyte orientation known from histology, and the transmural rate of change in myocyte orientation was dependent on LV size and thickness. In HV, comparison of cDTI parameters between systole and diastole revealed an increase in transmural gradient, combined with a significant re-orientation of sheetlet angle. In contrast, in HCM, myocyte gradient increased between phases, however sheetlet angulation retained a systolic-like orientation in both phases. Combined analysis with hypertensive patients revealed a proportional decrease in sheetlet mobility with increasing LVH. CONCLUSION In vivo DW-STEAM cDTI can characterise LV microstructural dynamics non-invasively. The transmural rate of change in myocyte angulation is dependent on LV size and wall thickness, however inter phase changes in myocyte orientation are unaffected by LVH. In contrast, sheetlet dynamics demonstrate increasing dysfunction, in proportion to the degree of LVH. Resolving technical limitations is key to advancing this technique, and improving the understanding of the role of microstructural abnormalities in cardiovascular disease expression.Open Acces

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected

Normal reference intervals for cardiac dimensions and function for use in echocardiographic practice: a guideline from the British Society of Echocardiography.

This guideline presents reference limits for use in echocardiographic practice, updating previous guidance from the British Society of Echocardiography. The rationale for change is discussed, in addition to how the reference intervals were defined and the current limitations to their use. The importance of interpretation of echocardiographic parameters within the clinical context is explored, as is grading of abnormality. Each of the following echo parameters are discussed and updated in turn: left ventricular linear dimensions and LV mass; left ventricular volumes; left ventricular ejection fraction; left atrial size; right heart parameters; aortic dimensions; and tissue Doppler imaging. There are several important conceptual changes to the assessment of the heart’s structure and function within this guideline. New terminology for left ventricular function and left atrial size are introduced. The British Society of Echocardiography has advocated a new approach to the assessment of the aortic root, the right heart, and clarified the optimal methodology for assessment of LA size. The British Society of Echocardiography has emphasized a preference to use, where feasible, indexed measures over absolute values for any chamber size

The Impact of Training Quantity on Structure-Function Relationships of the Cyclist's Heart

Structural and functional adaptations of the left ventricle (LV) in response to chronic exercise training termed the “athlete’s heart” (AH) are central to a road cyclist’s (RC) performance capacity. As a result, RC athletes complete very high training hours, which generate a stimulus for cardiac remodelling. In some cases, the profound adaptation observed in these athletes can mimic pathological processes, presenting a risk of false-positive identification of cardiomyopathy at pre-participation screening or during follow-up. Furthermore, emerging data suggest acute transient post-strenuous exercise reductions in LV systolic and diastolic function termed “exercise induced cardiac fatigue” (EICF) may be extended to short-term periods such as overload training where very high training hours and limited recovery exist (i.e. training camps and/or stage races). The magnitude and possible mechanism(s) responsible for persistent EICF in overload training, and implications for pre-participation screening/follow-up of RC are not fully understood. Based on this, the aims of this thesis were: 1) establish the impact of moderate and very high chronic training hours on structural, functional and mechanical remodelling of the road cyclist’s LV, 2) determine how the LV responds to variations in training hours across a competitive road cycling season, 3) assess the impact of short-term overload endurance training on LV structure-function-mechanical relationships of the road cyclist’s LV, and 4) evaluate the relationship between LV function and road cycling performance following short-term overload endurance training. Study 1 (Chapter 4) highlighted that LV eccentric hypertrophy is commonly presented by elite cyclists (EC) (35%), but not sub-elite cyclists (SEC) (3%). Increases in LV mass between non-athletes (NA) and SEC (133 ± 24 vs 163 ± 26 g, P<0.001) were predominantly driven by chamber expansion, whereas increased chamber concentricity between SEC and EC (5.85 ± 0.98 vs 7.11 ± 1.08 g/ml2/3, P<0.001) drove further LV mass development (133 ± 24 vs 210 ± 31 g, P<0.001). Marked structural remodelling in EC was also associated with a high prevalence of reduced (<52%) LV ejection fraction (LV EF) (12 %) and mildly reduced diastolic function. Study 2 (Chapter 5) established a progressive increase in LV mass between off-season and end-season in parallel with an accumulation of training hours in RC (143 ± 17 vs 162 ± 31, P<0.05), which was eccentric in nature. Although RC presented mildly decreased early diastolic function during the most rapid increase in training hours, both resting and in-exercise mechanics remained unchanged across all timepoints. In study 3 (chapter 6), 3-weeks of overload (OL) training elicited acute fatigue in RC, which was associated with dilatation of the LV (50.8 ± 2.9 vs 51.8 ± 3.2 mm, P<0.05), a decreased ability to augment LV EF (67 ± 5 vs 63 ± 3, P=0.056), and an increased atrial contribution to diastolic filling in-exercise (9 ± 3 vs 12 ± 2 cm/s, P<0.05). Decreased LV twist (17.7 ± 4.5 vs 15.3 ± 3.3, P<0.05) and global longitudinal strain (GL ɛ) (-20.2 ± 1.0 vs 19.2 ± 1.3, P= 0.063) are indicative of intrinsic contractile dysfunction and suggest similar mechanisms are involved in both acute and persistent EICF. The application of conventional and novel echocardiographic techniques have provided further understanding of normal physiological adaptation of the LV in response to short-, medium- and long-term high training hours in RC. These insights may lead to improvements in pre-participation screening and influence the training practices of this athlete group