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ContextBardet–Biedl syndrome (BBS) is a rare autosomal recessive syndromic obesity of childhood onset among many other features. To date, the excess risk of metabolic complications of severe early-onset obesity in BBS remains controversial. In-depth investigation of adipose tissue structure and function in link with detailed metabolic phenotype has not been investigated yet.ObjectiveTo investigate adipose tissue function in BBSDesignA prospective cross-sectional study.Main outcome measureTo determine if there are differences in insulin resistance, metabolic profile, adipose tissue function and gene expression in patients with BBS compared to BMI-matched polygenic obese controls.Method9 adults with BBS and 10 controls were recruited from the national centre for BBS, Birmingham, UK. An in-depth study of adipose tissue structure and function along with insulin sensitivity was performed using hyperinsulinemic-euglycemic clamp studies, adipose tissue microdialysis, histology and RNA sequencing, and measurement of circulating adipokines and inflammatory biomarkers.ResultsAdipose tissue structure, gene expression and in-vivo functional analysis between BBS and polygenic obesity cohorts were similar. Using hyperinsulinemic-euglycemic clamp and surrogate markers of insulin resistance, we found no significant differences in insulin sensitivity between BBS and obese controls. Furthermore, no significant changes were noted in an array of adipokines, cytokines and pro-inflammatory markers.ConclusionAlthough childhood-onset extreme obesity is a feature of BBS, detailed studies of insulin sensitivity and adipose tissue structure and function are similar to common polygenic obesity. This study adds to the literature by suggesting that it is the quality and quantity of adiposity not the duration that drives the metabolic phenotype.

Background Catheter ablation for atrial fibrillation is recommended for symptomatic patients after failed medical therapy. Ablation has a higher failure rate in obese patients, and both the prevalence of atrial fibrillation and obesity are increasing globally. The outcome of ablation can be improved if obese patients can achieve goal-oriented weight reduction prior to ablation. Conventional weight loss strategies however, can be difficult to access and can delay ablation, thereby risking a lower chance of maintaining sinus rhythm. Effective weight-loss medications, such as the glucagon-like peptide inhibitor-1 drugs, offer the potential for incremental impact on weight loss over a shorter period of time as a bridging therapy. The aim of this study is to assess the feasibility of using liraglutide, a glucagon-like peptide inhibitor-1, in producing weight loss in obese patients before catheter ablation. Methods The study is an open label, uncontrolled, prospective single centre feasibility study of daily liraglutide injections in the treatment of obese patients for at least 13 weeks before and 52 weeks after AF ablation. Adult patients with symptomatic AF whose body mass index ≥30 will be recruited from those planning to undergo ablation. Feasibility will be determined based on the recruitment rate, adherence to the medication and the amount of weight loss achieved over the study period. Exploratory outcomes include changes in atrial structure, function and fibrosis with weight loss evaluated by cardiac magnetic resonance imaging, electroanatomic mapping, and patient reported outcome measure. Discussion This study will allow us to determine whether the use of liraglutide in obese patients with atrial fibrillation undergoing ablation is feasible with adequate recruitment. The additional information on adherence and average weight loss over the study period will inform the design of a future definitive randomized controlled trial. Trial registration ClinicalTrials.gov (NCT05221229) Registered on 2 February 2022 (https://clinicaltrials.gov/ct2/show/NCT05221229) Trial funding Metchley Park Medical Society and University of Birmingham Starter Fellowship, British Heart Foundation Accelerator Grant, Abbott Investigator Initiated Study Grant.

Fabry disease (FD) is a rare lysosomal storage disorder resulting in myocardial sphingolipid accumulation which is detectable by cardiovascular magnetic resonance as low native T1. However, myocardial T1 contains signal from intramyocardial blood which affects variability and consequently measurement precision and accuracy. Correction of myocardial T1 by blood T1 increases precision. We therefore deployed a multicenter study of FD patients (n = 218) and healthy controls (n = 117) to investigate if blood-correction of myocardial native T1 increases the number of FD patients with low T1, and thus reclassifies FD patients as having cardiac involvement. Cardiac involvement was defined as a native T1 value 2 standard deviations below site-specific means in healthy controls for both corrected and uncorrected measures. Overall low T1 was 135/218 (62%) uncorrected vs. 145/218 (67%) corrected (p = 0.02). With blood-correction, 13/83 previously normal patients were reclassified to low T1. This reclassification appears clinically relevant as 6/13 (46%) of reclassified had focal late gadolinium enhancement or left ventricular hypertrophy as signs of cardiac involvement. Blood-correction of myocardial native T1 increases the proportion of FD subjects with low myocardial T1, with blood-corrected results tracking other markers of cardiac involvement. Blood-correction may potentially offer earlier detection and therapy initiation, but merits further prospective studies.

The aims of this study were to quantify preoperative myocardial fibrosis using late gadolinium enhancement (LGE), extracellular volume fraction (ECV%), and indexed extracellular volume (iECV) on cardiac magnetic resonance; determine whether this varies following surgery; and examine the impact on postoperative outcomes.Myocardial fibrosis complicates chronic severe primary mitral regurgitation and is associated with left ventricular dilatation and dysfunction. It is not known if this nonischemic fibrosis is reversible following surgery or if it affects ventricular remodeling and patient outcomes.A multicenter prospective study was conducted among 104 subjects with primary mitral regurgitation undergoing mitral valve repair. Cardiac magnetic resonance and cardiopulmonary exercise stress testing were performed preoperatively and ≥6 months after surgery. Symptoms were assessed using the Minnesota Living With Heart Failure Questionnaire.Mitral valve repair was performed for Class 2a indications in 65 patients and Class 1 indications in 39 patients. Ninety-three patients were followed up at 8.8 months (IQR: 7.4 months-10.6 months). Following surgery, there were significant reductions in both ECV% (from 27.4% to 26.6%; P = 0.027) and iECV (from 17.9 to 15.4 mL/mMitral valve surgery results in reductions in ECV% and iECV, which are surrogates of diffuse myocardial fibrosis, and preoperative iECV predicts the degree of postoperative remodeling irrespective of symptoms. (The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation; NCT02355418).

The wide overlap between the syndromes of chronic kidney disease (CKD) and chronic heart failure (HF) means that familiarity with the 2021 European Society of Cardiology guidelines is of importance to nephrologists. The common risk factors for the two syndromes together with the adverse cardiac structural remodelling associated with CKD means that many kidney disease patients experience breathlessness and fall within the HF phenotypes categorized in the guidelines. The management of HF is evolving rapidly leading to significant changes in the latest guideline iteration. The 2021 guidelines have changed from the 2016 version firstly by an increased focus on identifying the three phenotypes of HF to guide appropriate evidence-based management. Secondly, a new and simplified treatment algorithm for HF with reduced ejection fraction involving the rapid sequential initiation and up-titration of four ‘pillars’ of drug treatment—angiotensin-converting enzyme inhibitors or angiotensin-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and now, thanks to convincing trial data, sodium-glucose co-transporter 2 inhibitors. Thirdly, guidelines for device therapy have been changed with down-graded advice on indications for primary prevention implantable cardioverter defibrillator therapy for patients with non-ischaemic HF and for cardiac resynchronization therapy with left bundle branch block (LBBB) and a QRS duration

Cardiovascular magnetic resonance T1-mapping enables myocardial tissue characterisation, and is capable of quantifying both intracellular and extracellular volume. T1-mapping is conventionally performed in diastole, however, we hypothesised that systolic readout would reduce variability due to a reduction in myocardial blood volume. This study investigated whether T1-mapping in systole alters T1 values compared to diastole and whether reproducibility alters in atrial fibrillation compared to sinus rhythm. We prospectively identified 103 consecutive patients recruited to the Mitral FINDER study who had T1 mapping in systole and diastole. These patients had moderate or severe mitral regurgitation and a high incidence of ventricular dilatation and atrial fibrillation. T1, ECV and goodness-of-fit (R2) values of the T1 times were calculated offline using Circle cvi42 and in house-developed software. Systolic T1 mapping was associated with fewer myocardial segments being affected by artefact compared to diastolic T1 mapping [217/2472 (9%) vs 515/2472 (21%)]. Mean native T1 values were not significantly different when measured in systole and diastole (985 ± 26 ms vs 988 ± 29 respectively; p = 0.061) and mean post-contrast values showed similar good agreement (462 ± 32 ms vs 459 ± 33 respectively, p = 0.052). No clinically significant differences in ECV, native T1 and post-contrast T1 were identified between diastolic and systolic T1 maps in males versus females, or in patients with permanent atrial fibrillation versus sinus rhythm. A statistically significant improvement in R2 value was observed with systolic over diastolic T1 mapping in all analysed maps (n = 411) (96.2 ± 1.4% vs 96.0 ± 1.4%; p p p p p = 0.009]. In conclusion, myocardial T1 mapping is associated with similar T1 and ECV values in systole and diastole. Furthermore, systolic acquisition is less prone to gating artefact in arrhythmia.

Background and objectives In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone. Design, setting, participants, & measurements A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30–89 ml/min per 1.73 m2). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg). Results There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was −3.8 g (95% confidence interval, −8.1 to 0.5 g, P=0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (−0.4 m/s, 0.5 m/s, P=0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, P=0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, P=0.07). Conclusions Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD.

Aims To determine whether myocardial fibrosis and greyzone fibrosis (GZF) on cardiovascular magnetic resonance (CMR) is associated with ventricular arrhythmias in patients with coronary artery disease (CAD) and a left ventricular ejection fraction (LVEF) >35%. Methods and results In this retrospective study of CAD patients, GZF mass using the 3SD method (GZF3SD) and total fibrosis mass using the 2SD method (TF2SD) on CMR were assessed in relation to the primary, combined endpoint of sudden cardiac death, ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac arrest. Among 701 patients [age: 65.8 ± 12.3 years (mean ± SD)], 28 (3.99%) patients met the primary endpoint over 5.91 years (median; interquartile range 4.42–7.64). In competing risks analysis, a GZF3SD mass ≥5.0 g was strongly associated with the primary endpoint [subdistribution hazard ratio (sHR): 17.4 (95% confidence interval, CI 6.64–45.5); area under receiver operator characteristic curve (AUC): 0.85, P 35%, GZF3SD mass was strongly associated with the arrhythmic endpoint. These findings hold promise for its use in identifying patients with CAD and an LVEF >35% at risk of arrhythmic events., Graphical Abstract Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) was used to detect myocardial fibrosis in patients with coronary artery disease (CAD). As shown in the horizontal long axis (left upper panel) and short-axis views (left lower panel) of the left ventricle, areas of greyzone fibrosis are typically heterogeneous, often harbouring ‘channels’ in between areas of myocardial fibrosis. As shown in the survival curves (right upper panel), the proportional risk of the primary endpoint increased with increasing greyzone fibrosis mass using the 3SD method (GZF3SD). In comparison to left ventricular ejection fraction (LVEF) and total fibrosis mass, this risk, expressed in terms of subdistribution hazard ratios (sHRs) from competing risks analyses, was much higher for GZF3SD than for total fibrosis mass using the 2SD method, or LVEF (right lower panel). LV, left ventricle; RV, right ventricle.

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe (i) changes in multiple echocardiographic parameters; (ii) differences in rate of progression of three predominant genotypes; and (iii) the ability of changes in echocardiographic parameters to predict prognosis. Methods and results: We prospectively studied 877 ATTR-CM patients attending our centre between 2000 and 2020. Serial echocardiography findings at baseline, 12 months and 24 months were compared with survival. Overall, 565 patients had wild-type ATTR-CM and 312 hereditary ATTR-CM (201 with V122I; 90 with T60A). There was progressive worsening of structural and functional parameters over time, patients with V122I ATTR-CM showing more rapid worsening of left and right ventricular structural and functional parameters compared to both wild-type and T60A ATTR-CM. Among a wide range of echocardiographic analyses, including deformation-based parameters, only worsening in the degree of mitral (MR) and tricuspid regurgitation (TR) at 12- and 24-month assessments was associated with worse prognosis (change at 12 months: MR, hazard ratio 1.43 [95% confidence interval 1.14–1.80], p = 0.002; TR, hazard ratio 1.38 [95% confidence interval 1.10–1.75], p = 0.006). Worsening in MR remained independently associated with poor prognosis after adjusting for known predictors. Conclusion: In ATTR-CM, echocardiographic parameters progressively worsen over time. Patients with V122I ATTR-CM demonstrate the most rapid deterioration. Worsening of MR and TR were the only parameters associated with mortality, MR remaining independent after adjusting for known predictors.

The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted educational grants Background Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias. We sought to determine whether presence of MF on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts SCD and ventricular fibrillation / sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation. Methods In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of sudden cardiac death (SCD) and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation. Results Among 700 patients (age 68.0 ± 12.0yrs [mean ± SD]), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over 6.93 yrs (median; interquartile range 5.82-9.32). MFVA predicted SCD (hazard ratio [HR]: HR:26.3 [95% confidence interval [CI] 3.70-3337]; negative predictive value: 100%). In competing risks analyses, MFVA also predicted the arrhythmic endpoint (subdistribution [sHR]: 19.9 [95% CI 6.40-61.9]; negative predictive value:98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) > 17 g was associated with highest risk of SCD (HR: 44.6;95% CI 6.12-5685) and the arrhythmic endpoint (sHR: 30.3 [95% CI 9.60-95.8]). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint. Conclusions In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.

Background Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertension and left ventricular hypertrophy. The contributory role of other mediators important in the development of cardiovascular disease in ESRD has not been studied. The aim of this study was to examine the prevalence of CMD in a cohort of kidney transplant candidates and to look for associations of CMD with markers of anaemia, bone mineral metabolism and chronic inflammation. Methods Twenty-two kidney transplant candidates with ESRD were studied with myocardial contrast echocardiography, Doppler CFVR assessment and serum multiplex immunoassay analysis. Individuals with diabetes, uncontrolled hypertension or ischaemic heart disease were excluded. Results 7/22 subjects had CMD (defined as CFVR Conclusions Among kidney transplant candidates with ESRD, there is a high prevalence of CMD, despite the absence of traditional risk factors. Anaemia may be a potential driver of microvascular dysfunction in this population and requires further investigation.

Supplemental Digital Content is available in the text., Kidney donation reduces renal function by ≈30% allowing study of the cardiovascular effects of a reduced estimated glomerular filtration rate without comorbidities. We report 5-year results of a longitudinal, parallel-group, blinded end-point study of living kidney donors (n=50) and healthy controls (n=45). The primary end point, left ventricular mass, was measured using cardiac magnetic resonance. Secondary end points, 24-hour ambulatory blood pressure, and pulse wave velocity were measured using validated blood pressure monitors and the SphygmoCor device. Effect sizes were calculated as differences between change from baseline in the donor and control groups. In donors, estimated glomerular filtration rate was 95±15 mL/min per 1.73 m2 at baseline (predonation) and 67±14 mL/min per 1.73 m2 at 5 years. In controls, there was a −1±2 mL/min per 1.73 m2 decline per annum. Change in left ventricular mass at 5 years was not significantly different between donors and controls (mean difference, +0.40 g [95% CI, −4.68 to 5.49] P=0.876), despite an initial increase in mass in donors compared with controls at 12 months. Pulse wave velocity, which increased in donors at 12 months, returned to levels not different from controls at 5 years (mean difference, −0.24 m/s [95% CI, −0.69 to 0.21]). Change in ambulatory systolic blood pressure was not different in donors compared with controls (mean difference, +1.91 mm Hg [95% CI, −2.72 to 6.54]). We found no evidence that the reduction in estimated glomerular filtration rate after kidney donation was associated with a change in left ventricular mass detectable by magnetic resonance imaging at 5 years.

Aims This study aimed to examine if the cardiac changes associated with uraemic cardiomyopathy are reversed by renal transplantation. Methods and results MEDLINE, Embase, OpenGrey, and the Cochrane Library databases were searched from 1950 to March 2020. The primary outcome measure was left ventricular mass index. Secondary outcome measures included left ventricular dimensions and measures of diastolic and systolic function. Studies were included if they used any imaging modality both before and after successful renal transplantation. Data were analysed through meta‐analysis approaches. Weight of evidence was assessed through the Grading of Recommendations Assessment, Development and Evaluation system. Twenty‐three studies used echocardiography, and three used cardiac magnetic resonance imaging as their imaging modality. The methodological quality of the evidence was generally poor. Four studies followed up control groups, two using cardiac magnetic resonance imaging and two using echocardiography. Meta‐analysis of these studies indicated that there was no difference in left ventricular mass index between groups following transplantation {standardized mean difference −0.07 [95% confidence interval (CI) −0.41 to 0.26]; P = 0.67}. There was also no difference observed in left ventricular ejection fraction [mean difference 0.39% (95% CI −4.09% to 4.87%); P = 0.86] or left ventricular end‐diastolic volume [standardized mean difference −0.24 (95% CI −0.94 to 0.45); P = 0.49]. Inconsistent reporting of changes in diastolic dysfunction did not allow for any meaningful analysis or interpretation. Conclusions The evidence does not support the notion that uraemic cardiomyopathy is reversible by renal transplantation. However, the evidence is limited by methodological weaknesses, which should be considered when interpreting these findings.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor (EGF) receptor (HER) 2-positive targeted treatment (e.g. trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

Patients with carcinoid heart disease (CHD) are referred for valve replacement if they have severe symptomatic disease or evidence of right ventricular (RV) failure and an anticipated survival of at least 12 months. Data are lacking, however, on the role of transthoracic echocardiography in predicting outcomes. We carried out a retrospective, single-centre cohort study of patients with a biopsy-confirmed neuroendocrine tumour (NET) and CHD undergoing valve replacement for severe valve disease and symptoms of right heart failure. The aim was to identify factors associated with postoperative mortality, both within one year of surgery and during long-term follow-up. Of 88 patients with NET, 49 were treated surgically (mean age: 64.4 ± 7.6 years; 55% male), of whom 48 had a bioprosthetic tricuspid valve replacement for severe tricuspid regurgitation; 39 patients had a pulmonary valve replacement. Over a median potential follow-up of 96 months (interquartile range: 56–125), there were 37 deaths, with 30-day and one-year mortality of 14% (n = 7) and 39% (n = 19), respectively. A significant relationship between RV size and one-year mortality was observed, with 57% of those with severe RV dilatation dying within a year of surgery, compared to 33% in those with normal RV size (p = 0.039). This difference remained significant in the time-to-event analysis of long-term survival (p = 0.008). RV size was found to reduce significantly with surgery (p < 0.001). Those with persisting RV dilatation (p = 0.007) or worse RV function (p = 0.001) on postoperative echocardiography had significantly shorter long-term survival. In this single-centre retrospective study of patients undergoing surgery for CHD, increasingly severe RV dilatation on preoperative echocardiography predicted adverse outcomes, yielding a doubling of the one-year mortality rate relative to normal RV size. These data support the possibility that early surgery might deliver greater long-term benefits in this patient cohort.

The validity and reproducibility of systolic function assessment in patients with atrial fibrillation (AF) using cardiac magnetic resonance, echocardiography, nuclear imaging and computed tomography is unknown. A prospectively-registered systematic review was performed, including 24 published studies with patients in AF at the time of imaging and reporting validity or reproducibility data on left ventricular systolic parameters (PROSPERO: CRD42018091674). Data extraction and risk of bias were performed by 2 investigators independently and synthesized qualitatively. In 3 cardiac magnetic resonance studies (40 AF patients), left ventricular ejection fraction and stroke volume measurements correlated highly with catheter angiography (r ≥0.85), and intra- and/or interobserver variability were low. From 3 nuclear studies (171 AF patients), there were no external validation assessments but intra and/or interobserver and intersession variability were low. In 18 echocardiography studies (2,566 AF patients), 2 studies showed high external validity of global longitudinal strain and tissue Doppler s' with angiography-derived dP/dt (r ≥0.88). Global longitudinal strain and myocardial performance index were both associated with adverse cardiovascular events. Reproducibility of echocardiography was better when selecting an index-beat (where 2 preceding R-to-R intervals are similar) compared to averaging of consecutive beats. There were no studies relating to computed tomography. Most studies were small and biased by selection of patients with good quality images, limiting clinical extrapolation of results. The validity of systolic function measurements in patients with AF remains unclear due to the paucity of good-quality data.

Funding Acknowledgements Type of funding sources: None. BACKGROUND The ‘grayzone’ of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs). OBJECTIVES To determine whether GZF predicts SCD and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of LVEFs. METHODS In this retrospective study of CAD patients, myocardial fibrosis presence on visual assessment (MFVA) and GZF mass in patients with MFVA was assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs. RESULTS Among 979 patients (age: 65.8 ± 12.3 yrs [mean ± SD]), 29(2.96%) suffered a SCD and 80(8.17%) met the arrhythmic endpoint over 5.82 years (median; interquartile range: 4.1-7.3). In the whole cohort, MFVA was strongly associated with SCD (hazard ratio [HR]:10.1, 95% CI 1.42-1278.9) and the arrhythmic endpoint (HR:28.0, 95% CI 4.07-3525.4). In competing risks analyses, associations between LVEF 5.0 g was strongly associated with SCD (sHR:10.8, 95% CI 3.74-30.9) and the arrhythmic endpoint (sHR:7.40, 95% CI 4.29-12.8). Associations between LVEF CONCLUSIONS In CAD patients, MFVA plus quantified GZF3SD mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter defibrillators, assessment of MFVA followed by quantification of GZF3SD mass may be preferable to LVEF. Abstract Figure.

Background Epidemiological studies suggest that black, Asian and minority ethnic (BAME) patients may be at risk of worse outcomes from Coronavirus-19 (COVID-19) but the pathophysiological drivers for this association are unknown. This study sought to investigate the relationship between findings on echocardiography, mortality and race in COVID-19 pneumonia. Methods This was a multicenter, retrospective, observational study including 164 adults (61±13years; 78% male; 36% BAME) hospitalized with COVID-19 undergoing echocardiography between March 16 and May 9, 2020 at 3 days (IQR 2 – 5) from admission. The primary outcome was all-cause mortality. Results After a median follow up of 31 days (IQR 14 – 42 days), 58 (35%) patients had died. The right ventricle (RV) was dilated in 62 (38%) patients, and 58 (35%) patients had RV systolic dysfunction. Only 2 (1%) patients had left ventricular (LV) dilatation and 133 (81%) had normal or hyperdynamic LV systolic function. Reduced tricuspid annulus planar systolic excursion was associated with elevated D-dimer (ρ = −0.18, p = 0.025) and high-sensitivity cardiac Troponin (ρ = −0.30, p < 0.0001). Reduced RV systolic function (HR, 1.80; 95% CI, 1.05 – 3.09; p = 0.032) was an independent predictor of all-cause mortality after adjustment for demographic and clinical risk factors. Comparing white and BAME individuals, there were no differences in echocardiography findings, biomarkers or mortality. Conclusions In patients hospitalized with COVID-19 pneumonia, reduced RV systolic function is prevalent and associated with all-cause mortality. There is however, no racial variation in the early findings on echocardiography, biomarkers or mortality., This is the first study to assess the influence of race on echocardiographic findings in patients hospitalized with COVID-19 disease. In high-risk patients hospitalized with advanced COVID-19 disease, right ventricular (RV) dilatation and dysfunction are common; RV dysfunction (measured using the simple standard measures FAC and TAPSE) is independently associated with early mortality, and is associated with elevated D-dimer and high-sensitivity cardiac Troponin. There are, however, no racial differences in echocardiographic findings, biomarkers, or mortality.

Objectives A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance. Background CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown. Methods A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T1 mapping (biomarker of diffuse fibrosis), T2 mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro–B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography. Results Native myocardial T1 times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p Conclusions Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862 )

Background Moderate or severe tricuspid regurgitation (TR) recurs in up to one-third of patients within 8 years of surgical annuloplasty repair. Reoperation often carries high risk with poor outcomes. Transcatheter valve-in-ring repair is an emerging alternative treatment. However, residual regurgitation is frequent and may necessitate further procedures. Case summary A 52-year-old female was diagnosed with severe rheumatic valvular heart disease. The patient underwent mechanical aortic and mitral valve replacement. Additionally, tricuspid repair was performed using a semi-rigid annuloplasty ring (28 mm Edwards Physio Tricuspid). Within 2 years, the patient developed recurrent, isolated severe symptomatic TR, with progressive right ventricular dilatation. The patient was considered prohibitive risk for redo surgery and unsuitable for cardiac transplantation. She underwent percutaneous valve-in-ring transcatheter heart valve (THV) implantation using a 29 mm Sapien S3 (Edwards Lifesciences, CA, USA) valve. Persistent severe residual para-ring TR warranted a further procedure to deploy vascular plugs, significantly reducing the TR to a mild jet with symptomatic improvement. Discussion Valve-in-ring THV implantation for failed surgical tricuspid annuloplasty repair is a rare procedure reserved for symptomatic patients at high or prohibitive risk for reoperation. Significant residual TR is a commonly encountered problem with incomplete annuloplasty rings following valve-in-ring procedures and may occur either intra-ring between the THV and the ring or para-ring. Implantation of vascular occlusion devices can be used to successfully treat residual TR at either location with good outcomes at 6-month follow-up. Further work is required to determine the longevity of this treatment.

Since cardiac ultrasound was introduced into medical practice around the middle twentieth century, transthoracic echocardiography has developed to become a highly sophisticated and widely performed cardiac imaging modality in the diagnosis of heart disease. This evolution from an emerging technique with limited application, into a complex modality capable of detailed cardiac assessment has been driven by technological innovations that have both refined ‘standard’ 2D and Doppler imaging and led to the development of new diagnostic techniques. Accordingly, the adult transthoracic echocardiogram has evolved to become a comprehensive assessment of complex cardiac anatomy, function and haemodynamics. This guideline protocol from the British Society of Echocardiography aims to outline the minimum dataset required to confirm normal cardiac structure and function when performing a comprehensive standard adult echocardiogram and is structured according to the recommended sequence of acquisition. It is recommended that this structured approach to image acquisition and measurement protocol forms the basis of every standard adult transthoracic echocardiogram. However, when pathology is detected and further analysis becomes necessary, views and measurements in addition to the minimum dataset are required and should be taken with reference to the appropriate British Society of Echocardiography imaging protocol. It is anticipated that the recommendations made within this guideline will help standardise the local, regional and national practice of echocardiography, in addition to minimising the inter and intra-observer variation associated with echocardiographic measurement and interpretation.

Background and objectives The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics. Design, setting, participants, & measurements Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months. Results A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, −1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, −0.7 to 2.0) in controls. The between-group difference was −0.5 mm Hg (95% confidence interval, −2.8 to 1.7; P=0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, −0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, −0.2 to 0.3; P=0.49). Conclusions Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls. Clinical Trial registry name and registration number NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924).

The aim of this study was to characterize the echocardiographic phenotype of patients with COVID-19 pneumonia and its relation to biomarkers. Seventy-four patients (59 ± 13 years old, 78% male) admitted with COVID-19 were included after referral for transthoracic echocardiography as part of routine care. A level 1 British Society of Echocardiography transthoracic echocardiography was used to assess chamber size and function, valvular disease, and likelihood of pulmonary hypertension. The chief abnormalities were right ventricle (RV) dilatation (41%) and RV dysfunction (27%). RV impairment was associated with increased D-dimer and C-reactive protein levels. In contrast, left ventricular function was hyperdynamic or normal in most (89%) patients.

Acromegaly is disease associated with a specific cardiomyopathy. Hitherto, it has been widely understood that acromegaly carries an increased risk of arrhythmia. In this review we show that evidences are limited to a small number of case–control studies that reported increased rates of premature ventricular beats (PVB) but no more significant arrhythmia. In contrast, there are several studies that have reported impaired preclinical markers of arrhythmia, including reduced heart rate variability, increased late potentials, QT interval dispersion, impaired heart rate recovery after physical exercise and left ventricular dysynchrony. Whilst these markers are associated with an adverse cardiovascular prognosis in the general population, they do not have a high independent positive predictive accuracy for arrhythmia. In acromegaly, case reports have described sudden cardiac death, ventricular tachyarrhythmia and advanced atrio-ventricular block that required implantation of a cardio-defibrillator or permanent pacemaker. Treatment with somatostatin analogues can reduce cardiac dysrhythmia in some cases by reducing heart rate, PVBs and QT interval. Pegvisomant reduces mean heart rate. Pasireotide is associated with QT prolongation. In the absence of good quality data on risk of arrhythmia in acromegaly, the majority of position statements and guidelines suggest routine 12-lead electrocardiography (ECG) and transthoracic echocardiography (TTE) in every patient at diagnosis and then follow up dependent on initial findings.

Background Although consensus-based guidelines support noninvasive stress testing prior to orthotopic liver transplantation (OLT), the optimal screening strategy for assessment of coronary artery disease in patients with end-stage liver disease (ESLD) is unclear. This study sought to determine the relative predictive value of coronary risk factors, functional capacity, and single photon emission computed tomography (SPECT) on major adverse cardiovascular events and all-cause mortality in liver transplantation candidates. Methods Prior to listing for transplantation, 404 consecutive ESLD patients were referred to a University hospital for cardiovascular (CV) risk stratification. All subjects met at least one of the following criteria: inability to perform > 4 METs by history (62%), insulin-treated diabetes mellitus (53%), serum creatinine > 1.72 mg/dL (8%), history of MI, PCI or CABG (5%), stable angina (3%), cerebrovascular disease (1%), peripheral vascular disease (1%). Subjects underwent Technetium-99m SPECT with multislice coronary artery calcium scoring (CACS) using exercise treadmill or standard adenosine stress in those unable to achieve 85% maximal heart rate (Siemens Symbia T16). Abnormal perfusion was defined as a summed stress score (SSS) ≥ 4. Results Of the 404 patients, 158 (age 59 ± 9 years; male 68%) subsequently underwent transplantation and were included in the primary analysis. Of those, 50 (32%) died after a mean duration follow-up of 5.4 years (maximal 10.9 years). Most deaths (78%) were attributed to noncardiovascular causes (malignancy, sepsis, renal failure). Of the 32 subjects with abnormal perfusion (20%), nine (6%) had a high-risk perfusion abnormality defined as a total perfusion defect size (PDS) ≥ 15% and/or an ischemic PDS ≥ 10%. Kaplan–Meier survival curves demonstrated abnormal perfusion was associated with increased CV mortality (generalized Wilcoxon, P = 0.014) but not all-cause death. Subjects with both abnormal perfusion and an inability to exercise > 4 METs had the lowest survival from all-cause death (P = 0.038). Abnormal perfusion was a strong independent predictor of CV death (adjusted HR 4.2; 95% CI 1.4 to 12.3; P = 0.019) and MACE (adjusted HR 7.7; 95% CI 1.4 to 42.4; P = 0.018) in a multivariate Cox regression model that included age, sex, diabetes, smoking and the ability to exercise > 4 METs. There was no association between CACS and the extent of perfusion abnormality, nor with outcomes. Conclusions Most deaths following OLT are noncardiovascular. Nonetheless, abnormal perfusion is prevalent in this high-risk population and a stronger predictor of cardiovascular morbidity and mortality than functional status. A combined assessment of functional status and myocardial perfusion identifies those at highest risk of all-cause death. (Exercise Capacity and Single Photon Emission Computed Tomography in Liver Transplantation Candidates [ExSPECT]; ClinicalTrials.gov Identifier: NCT03864497).