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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).

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.

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 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 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).

Background Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk. No studies to date have investigated the presence of coronary microvascular dysfunction in living kidney donors. Methods 25 healthy controls and 23 living kidney donors were recruited and underwent assessment with transthoracic echocardiography, Doppler CFVR, myocardial contrast echocardiography and serum multiplex immunoassay panels. Results Doppler CFVR was significantly reduced in living kidney donors compared to controls (mean CFVR 3.4 ± 0.7 vs 3.8 ± 0.6, mean difference 0.4 95% confidence interval 0.03–0.8, p =.036). Quantitative myocardial contrast echocardiography showed a trend towards reduced coronary flow reserve in living kidney donors. Compared to controls, living kidney donors had higher serum high sensitivity C reactive peptide (hsCRP) and lower levels of uromodulin. Conclusions This is the first study of CFVR in living kidney donors. We have shown that the modest drop in estimated glomerular filtration rate in living kidney donors is associated with lower values of Doppler CFVR compared to controls, suggesting that isolated reductions in renal function may lead to altered microvascular function. The increase in hsCRP and reduction in uromodulin suggests that chronic subclinical inflammation may contribute to altered microvascular function in this population., Highlights • Coronary flow velocity reserve is reduced in living kidney donors compared to controls. • Markers of inflammation are elevated in living kidney donors. • Inflammation may cause coronary microvascular dysfunction in living kidney donors. • Living kidney donors need aggressive cardiovascular risk factor management.

Background Fabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database. Results Indications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p p = 0.004, NSVT: HR 3.1, p Conclusion This study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more ‘arrhythmogenic’ than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement.

Background Mitral regurgitation (MR) is commonly observed following acute myocardial infarction (MI). Localised left ventricular (LV) remodelling in the region of papillary muscles together with impaired myocardial contractility promote MR. There is a paucity of long-term follow-up studies to determine whether the severity of MR observed post-MI, changes with time. Purpose This study retrospectively followed up patients with MR detected following acute MI (AMI) to investigate changes in MR severity with time and assess for pre-discharge predictors of MR regression or progression. Methods Clinical records of 1000 patients admitted with AMI between 2016 and 2017 to a single centre were retrospectively interrogated. One hundred and nine patients met the inclusion criteria of MR on pre-discharge transthoracic echocardiography (TTE) and follow-up TTE scans. Echocardiographic parameters were investigated to determine predictors of progression or regression at follow-up. Patients were divided according to those who had early follow-up TTE (within 1-year) and late follow-up TTE (beyond 1-year). Results Early follow-up TTE was performed in 73 patients at a median of 6 (IQR 3–9) months. Patients had a mean age of 69±13 years and were predominantly male 50/73 (68%). At baseline, relative MR severities were: 49/73 (67%) mild MR, 23/73 (32%) moderate MR and 1 (1%) severe MR. At follow-up, MR had completely resolved in 18/73 (23%) patients, while 39/73 (53%) had mild MR, 15/73 (21%) moderate MR and 1 (1%) severe MR. Compared to patients with no resolution of MR, those with completel resolution were younger (mean age 62±16 vs 72±11 years; p=0.015) but there were no other significant differences between the groups. Resolution at early follow-up did not significantly influence long-term mortality rates. Late follow-up TTE was performed in 69 patients at a median 2.4 (IQR 2–3.2) years. Pre-discharge, 49/69 (71%) patients had mild MR and 20/69 (29%) moderate MR. At follow-up, MR had completely resolved in 18/69 (26%), and amongst patients with persistent MR, proportion of severities were: 37/69 (54%) mild MR, 11/69 (16%) moderate MR and 3/69 (4%) severe MR. Patients with progression of mild MR were more likely to have lower left ventricular ejection fraction (LVEF: 47±15 vs 57±12%; p=0.010) and greater indexed left ventricular end-systolic volume (LVESVi: 37±23 vs 25±14 ml/m2; p Conclusion MR observed following AMI completely resolved in approximately one-quarter of patients at 6-month and 2-year follow-up. Progression of mild MR at long-term follow-up appears to be associated with increased mortality and is predicted by lower LVEF and greater LVESVi pre-discharge. Funding Acknowledgement Type of funding sources: None.

Fabry disease (FD) is a lysosomal storage disorder characterised by a deficiency in the enzyme α-galactosidase A resulting in sphingolipid deposition which causes progressive cardiac, renal, and cerebral manifestations. The case illustrates a patient with FD who died suddenly, and medical examination demonstrated myocardial scarring and prior infarction. Angina is a frequent symptom in FD. Our own data are consistent with registry data indicating a high prevalence of risk factors for coronary artery disease (CAD) in FD that may accelerate conventional atherosclerosis. Patients with FD also have a higher high-density lipoprotein (HDL)/total cholesterol (T-Chol) ratio which may further accelerate atherosclerosis through expression of early atherosclerotic markers. Patients with FD may develop CAD both via classical atherosclerosis and through formation of thickened fibrocellular intima containing fibroblasts with storage of sphingolipids. Both mechanisms occurring together may accelerate coronary stenosis, as well as alter myocardial blood flow. Our data supports limited data that, although coronary flow may be reduced, the prevalence of epicardial coronary stenosis is low in FD. Microvascular dysfunction and arterial wall stress from sphingolipid deposition may form reactive oxygen species (ROS) and myeloperoxidase (MPO), key atherosclerotic mediators. Reduced myocardial blood flow in FD has also been demonstrated using numerous imaging modalities suggesting perfusion mismatch. This review describes the above mechanisms in detail, highlighting the importance of modifying cardiovascular risk factors in FD patients who likely develop accelerated atherosclerosis compared to the general population.

Data were collected on patients admitted to the Queen Elizabeth Hospital Birmingham with type-1 myocardial infarction during 2016 and 2017 inclusively, who were treated by percutaneous intervention and had pre-discharge transthoracic echocardiography. The data were obtained from prospectively maintained hospital databases and records. Echocardiography was performed and reported contemporaneously by accredited echocardiographers. The purpose was to understand the prevalence and characteristics of mitral regurgitation (MR) after acute MI, including patients with ST-elevation (STEMI) and non-ST elevation MI (NSTEMI). MR was observed in 294/1000 patients with the following relative severities: mild = 76%, moderate = 21%, severe = 3% [1]. MR was graded by multiparametric quantification including proximal isolvelocity surface area (PISA), vena contracta (VC), effective regurgitant orifice area (EROA) and regurgitant volume (RVol). Amongst all patients with MR (n=294), PISA was performed in 89/294 (30%), VC 75/294 (26%), EROA in 53/294 (18%) and RVol in 26/294 (9%). Amongst patients with moderate or severe MR (n=70), PISA was performed in 57/70 (81%), VC in 55/70 (79%), EROA in 46/70 (66%) and RVol in 25/70 (36%). Characteristics of MR following acute MI were also assessed including frequency of reported leaflet thickness (259/294 = 88%) and mitral annular calcification (102/294 = 35%). Furthermore, the effect of MI on pre-existing MR was investigated and patients with pre-existing MR who continue to have MR after acute MI were found to have progression of MR by one grade in approximately 25% of cases. Finally, using Cox proportional hazards univariate analysis, significant factors associated with mortality in patients with MR post-MI include age (HR 1.065; 95% CI 1.035-1.096; p

Hypertrophic cardiomyopathy (HCM) is common, inherited and characterised by unexplained thickening of the myocardium. The British Society of Echocardiography (BSE) has recently published a minimum dataset for transthoracic echocardiography detailing the core views needed for a standard echocardiogram. For patients with confirmed or suspected HCM, additional views and measurements are necessary. This guideline, therefore, supplements the minimum dataset and describes a tailored, stepwise approach to the echocardiographic examination, and echocardiography's position in the diagnostic pathway, before advising on the imaging of disease complications and invasive treatments.

Coronavirus disease 2019 (COVID-19) was initially regarded as a disease of the lungs, which manifests as an acute respiratory illness and pneumonia, although more recently cardiac complications have been well-characterised. Serological cardiac biomarkers have been used to define acute myocardial injury, with significant elevation of high-sensitivity cardiac troponin (hs-cTn) associated with poor prognosis. Accordingly, 20–25% patients with acute myocardial injury (as defined by an elevated hs-cTn greater than the 99th percentile) have clinical signs of heart failure and increased mortality. An important outstanding clinical question is how best to determine the extent and nature of cardiac involvement in COVID-19. Non-invasive cardiac imaging has a well-established role in assessing cardiac structure and function in a wide range of cardiac diseases. It offers the potential to differentiate between direct and indirect COVID-19 effects upon the heart, providing incremental diagnostic and prognostic utility beyond the information yielded by elevated cardiac biomarkers in isolation. This review will focus on the non-invasive imaging assessment of cardiac involvement in COVID-19.

Funding Acknowledgements Type of funding sources: None. BACKGROUND Clinical guidelines adopt LVEF cut-offs OBJECTIVES To determine whether myocardial fibrosis (MF) and grayzone fibrosis (GZF) on cardiovascular magnetic resonance (CMR) is associated with ventricular arrhythmias in patients with coronary artery disease (CAD) and a LVEF≥35%. METHODS 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 SCD, ventricular tachycardia, ventricular fibrillation or resuscitated cardiac arrest. RESULTS Among 701 patients (age: 65.8 ± 12.3 yrs [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% CI 6.64-45.5]); area under receiver operator characteristic curve [AUC]: 0.85, p < 0.001). A weaker association was observed for TF2SD mass ≥ 23 g (HR: 10.4 [95% CI 4.22-25.8]; AUC: 0.80, p < 0.001). The range of sHRs for GZF3SD mass (1 to 526.6) was wider than for TF2SD mass (1 to 37.6). CONCLUSIONS In CAD patients with a LVEF≥35%, GZF3SD mass was strongly associated with the arrhythmic endpoint. These findings hold promise for its use in identifying patients with CAD and a LVEF≥35% at risk of arrhythmic events. Abstract Figure.

Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m2. Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ± 2% vs. 24 ± 2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ± 25 vs. 1002 ms ± 30, p = 0.014; ShMOLLI 974 ms ± 39 vs. 992 ms ± 33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ± 24 vs. 63 ± 20 ml/m2, p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ± 38 to 83 g/m2 ± 23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD., Highlights • ECV is elevated in ESKD suggesting the elevated myocardial T1 times observed are indicative of diffuse interstitial fibrosis. • The contribution of myocardial oedema towards elevated T1 times and ECV cannot be excluded in ESKD. • Native T1 times is a stable and reproducible biomarker of fibrosis.

Mitral regurgitation (MR) following acute myocardial infarction (AMI) worsens prognosis and reports of prevalence vary significantly. The objective was to determine prevalence, risk factors, and outcomes related to MR following AMI. We identified 1000 consecutive patients admitted with AMI in 2016/17 treated by percutaneous coronary intervention with pre-discharge transthoracic echocardiography. MR was observed in 294 of 1000 (29%), graded as mild (n = 224 [76%]), moderate (n = 61 [21%]) and severe (n = 9 [3%]). Compared with patients without MR, patients with MR were older (70 ± 12 vs 63 ± 13 years; p0.001), with worse left ventricular ejection fraction (LVEF) (52 ± 15% vs 55 ± 11%; p0.001) and creatinine clearance (69 ± 33 ml/min vs 90 ± 39 ml/min; p0.001). They also had higher rates of hypertension (64% vs 55%; p = 0.012), heart failure (3.4% vs 1.1%; p = 0.014), previous MI (28% vs 20%; p = 0.005) and severe flow-limitation in the circumflex (50% vs 33%; p0.001) or right coronary artery (51% vs 42%; p = 0.014). Prevalence and severity of MR were unaffected by AMI subtype. Revascularization later than 72 hours from symptom-onset was associated with increased likelihood of MR (33% vs 25%; p = 0.036) in patients with non-ST elevation myocardial infarction (NSTEMI). After a mean of 3.2 years, 56 of 288 (19%) patients with untreated MR died. Age and LVEF independently predicted mortality. The presence of even mild MR was associated with increased mortality (p = 0.029), despite accounting for confounders. In conclusion, MR is observed in over one-quarter of patients after AMI and associated with lower survival, even when mild. Prevalence and severity are independent of MI subtype, but MR was more common with delayed revascularization following NSTEMI.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a β-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, −1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, −2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.

ObjectiveApproximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR.MethodsParticipants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR.ResultsOf 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; pConclusionsThere may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): (1) University Hospitals Birmingham Charity (2) Metchley Park Medical Society Introduction Coronary microvascular dysfunction (CMD) is common among patients with end-stage renal disease (ESRD) and confers poor prognosis. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and can be reliably measured using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as hypertension and left ventricular hypertrophy (LVH). Anaemia is prevalent in ESRD but the association between haemoglobin and CFVR in ESRD has not been studied. Purpose To assess if CFVR is related to haemoglobin among patients with ESRD. Methods 22 subjects with ESRD and awaiting kidney transplant (8 pre-dialysis and 14 on peritoneal dialysis) were studied with adenosine 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 (32%) of subjects had CMD (defined as CFVR CFVR was significantly lower in subjects with CMD (1.6 ± 0.2 vs 3.2 ± 0.9, p Conclusions Among our cohort of ESRD patients awaiting kidney transplant, there was a high prevalence of CMD despite well controlled blood pressure and no significant LVH. Subjects with CMD had significantly lower haemoglobin than subjects without CMD. Reduced haemoglobin causes impaired oxygen carrying capacity to the myocardium, which may lead to microvascular ischaemia and adverse microvascular remodelling, causing CMD. Thus, anaemia may be a potentially correctible driver of CMD in ESRD. This association needs to be confirmed in larger studies. Abstract Figure 1

Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P mean 13.6% [6.3–18.8], P mean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P 2max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418

Introduction: The mechanisms linking obesity to increased mortality in patients with coronavirus-disease 2019 (COVID-19) are unclear. Hypothesis: We hypothesised that obesity would be associated with adverse right ventricular (RV) remodelling and function which might be further exacerbated by COVID-19 associated increases in RV afterload/demand. Methods: We used echocardiography and computed tomography to establish links between RV dimensions and function and bodyweight in patients with severe COVID-19. In obese and non-obese participants without COVID-19, we used cardiovascular magnetic resonance to define the effects of obesity upon RV volumes, energetics, systolic function and stress reserve. Results: In patients with severe COVID-19, increasing bodyweight was associated with disproportionate RV dilatation (n=26, echocardiography, R=0.42, P=0.03, CT n=34, R=0.23, P=0.004) and impairment of RV systolic function (fractional area change (FAC) R=-0.45, P=0.04); obesity (BMI >30kg/m2) was associated with a 32% reduction in RV FAC (P=0.03). Similar associations were seen in a validation cohort (n=91, all P2 ) was associated with RV remodelling, impaired cardiac energetics (PCr/ATP ratio 23% lower, P2 , n=27) had impaired RV diastolic filling rate at rest (P Conclusions: Increasing body weight is associated with both significant alterations in RV volumes, systolic function and stress responses which are mitigated with weight loss and also with disproportionate RV dilatation and dysfunction in severe COVID-19. RV dysfunction is a modifiable mechanism which might link obesity to adverse outcomes in patients with COVID-19 and other disorders stressing the right heart.

Background Cardiac involvement of Fabry disease (FD) includes left ventricular hypertrophy (LVH), inflammation, arrhythmia and sudden death. There are limited data regarding potential risk predictors and no definitive criteria exist to guide implantation of cardiac devices for primary prevention. Despite phenotypic similarities between FD and hypertrophic cardiomyopathy (HCM), FD is specifically excluded from the ESC sudden cardiac death risk prediction tool used for HCM. Purpose To evaluate differences in device implantation and arrhythmic burden between advanced Fabry cardiomyopathy and HCM. Methods This multi-centre, retrospective study including genetically confirmed FD and age/gender-matched HCM patients all of whom had an implantable cardioverter defibrillator (ICD). Data was collected prior to device implantation on disease characteristics, biomarkers and CMR imaging. Arrhythmia burden and changes in therapy were captured following implantation. Results Of the UK FD population under follow-up, 50/880 had an ICD implanted (80% males, 51% non-classical mutation, mean age at device implantation 57±12 years). A comparator group included 64 age- and gender-matched HCM patients (67% males, mean age at implant 46±39 years). Baseline LV mass was greater in FD (291±97g/m2 vs 218±78g/m2, p=0.012). FD patients had higher troponin (95 vs 19ng/l, p Indications for ICD insertion in FD included: presumed HCM dual pathology 14%, symptomatic NSVT 18%, asymptomatic NSVT 24%, co-existing long QT 2%, CRT-D 14%, no clear indication (primary prevention in the presence of multiple potential arrhythmic risk factors) 28%. All HCM patients were risk stratified and underwent device implantation based on an estimated 5-year SCD risk >4%. All FD patients had a SCD risk >4% using this risk calculator. Arrhythmia were more common in FD over shorter follow-up (37/50, 74% over 4.3±3.0 years vs 28/64 in HCM, 44% over 6.5±2.9 years, p=0.001). Notably, VT requiring anti-tachycardia pacing (ATP) +/− defibrillation therapy from the ICD was more frequent (FD: 14/50, 28% vs HCM: 8/64, 12%, p=0.055), as was immediate shock therapy for sustained VT (p=0.009, figure panel B). FD patients with arrhythmia were often older, had greater LV mass, a larger left atrium and a broader QRS duration. These clinical features tended to occur more frequently in FD than in the HCM group. Conclusion This study has shown that delivery of device therapy in Fabry cardiomyopathy is higher than in HCM. Despite similar rates of asymptomatic NSVT, a higher rate of ventricular arrhythmia requiring ATP/defibrillation therapy occurred in FD. Although both FD and HCM had similar risk percentages according to the ESC calculator, active troponitis in FD was double that of HCM. Funding Acknowledgement Type of funding source: None

Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson's biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e'). Results 160 patients (median age 75 years (IQR 69–82); 46% female) were included, with median heart rate 100 beats/min (IQR 86–112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Comparison for measurement of E/e' Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research UK

Background Previous studies of the incidence and severity of mitral regurgitation (MR) following acute myocardial infarction (MI) were limited by the study population (ST-elevation MI only), by diagnostic methods (lack of multiparametric quantification), or by the time-frame of study (late assessment post-MI). The true incidence of ischaemic MR (IMR) immediately following type 1 MI [non-ST-elevation (NSTEMI) and ST-elevation (STEMI)] patients in the modern era of universal early revascularisation remains unclear. Since even mild IMR confers a poor prognosis, factors which promote or protect against the development of MR require further evaluation. Purpose To determine the incidence, clinical and angiographic characteristics of patients with IMR following type 1 MI treated with PCI. Methods This was a single-centre study of 1000 consecutive, prospectively recruited patients admitted to the Queen Elizabeth Hospital Birmingham with type 1 MI who underwent PCI. Early inpatient transthoracic echocardiography (TTE) was performed by accredited echocardiographers using standard multiparametric quantification. Results MR was observed in 294/1000 patients (29.4%) post-MI, graded as mild (76%), moderate (21%) and severe (3%). Median time from symptom onset to PCI was 1 day (IQR 0–4) and to TTE 2 days (IQR 1–3). Compared to patients without MR (MR-), those with MR (MR+) were older (73±12 years vs 66±13 years; p MR+ patients were more likely to have severe disease in the left circumflex (LCx) (50% vs 33%; p Incidence of MR was equal (29%) amongst STEMI (126/431) and NSTEMI (168/569) patients. While the time to revascularisation did not affect the prevalence of MR following STEMI (linear regression analysis of door-to-balloon time in MR+ and MR- patients p=0.843), NSTEMI patients were more likely to develop MR if revascularisation was delayed (linear regression analysis of symptom onset to PCI time MR+ vs MR- p=0.061). Conclusion Almost 1/3 of patients with type 1 MI undergoing revascularisation have MR evident on pre-discharge TTE. Factors promoting MR include older age, male sex, HTN, HF, larger non-LAD territory infarct, and depressed LVEF. The incidence of MR following STEMIs and NSTEMIs is equal. Earlier revascularisation is unlikely to reduce MR in STEMI patients but may improve MR prevalence following NSTEMI. Funding Acknowledgement Type of funding source: None

Background Carcinoid heart disease (CHD) often complicates neuroendocrine tumours (NET). The prognosis of CHD without intervention is poor; 3 year survival is estimated at 31%. Surgical valve replacement is the only treatment for CHD, but is associated with high 30-day mortality (10–15%). Purpose The aim is to identify pre-operative transthoracic echocardiogram (PTTE) findings that could determine which patients have a high likelihood of post-surgical mortality at 1 year. Methods This retrospective observational cohort study recruited 88 patients with a confirmed diagnosis of CHD between 2005–19 at University Hospital Birmingham; 49 (56%) of these were treated surgically. Indications for surgery: stable NET, symptomatic severe valvular dysfunction, progressive RV dilatation or RV dysfunction, no significant comorbidities. All patients underwent a standard PTTE. PTTE parameters assessed: right ventricular (RV) size, RV function (qualitative), TAPSE, RV fractional area change, RV S wave velocity, left ventricular (LV) size, LV ejection fraction and valve velocities. Surgery was performed by a single surgical team with bioprosthetic valve replacements. Results Patients were followed up for a median of 15 months (IQR: 6–59) after surgery, during which time there were 33 deaths, giving a median survival time of 30 months (IQR: 7–85). Increasingly severe RV dilatation was significantly associated with shorter survival (p=0.032). The estimated survival rate at three years was 67% in those with normal RV size, compared to 24% in the severe RV group (Figure 1). RV basal diameter was assessed used ROC curve analysis for the outcome of one year survival and returned an area under the curve of 0.66 (SE=0.10). Youden's index identified RV diameter >4.8cm to be the optimal cut-off for identifying high-risk patients. One year mortality rates were 26% (7/27) vs. 75% (9/12) in those with RV basal diameter of ≤4.8 vs. >4.8cm (p=0.006). Conclusion A pre-operative right ventricular basal diameter >4.8cm is associated with a near three-fold increase in post-operative mortality at one year. These findings highlight the importance of regular imaging in order to optimise the timing of surgery in patients with CHD. Figure 1. Kaplan-Meier curve of post-op survival Funding Acknowledgement Type of funding source: None

Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4 years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were feasible from 86 patients with median CVF of 14.6% [IQR 7.4–20.3]. Fibrosis was present even in NYHA Class I patients (13.6% [6.3–18.8]), and was significantly higher than the 3.3% [2.6–6.1] obtained from 8 autopsy controls without cardiac disease (P Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although it did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV (27.4±3.3%) correlated with systolic (LVEF Rho=−0.22, P=0.029; LVESVi Rho=0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e' R=0.25, P=0.022), exercise capacity (%VO2max R=−0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Post-operatively, although LVEF remained normal (defined as >50%) in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Background Ischaemic mitral regurgitation (IMR) confers a poor prognosis. Transcatheter intervention may improve survival but benefit is likely to depend on severity of IMR relative to LV remodelling following myocardial infarction (MI). In theory, those with “discordant” IMR (significant regurgitant volume without severe LV dilatation or impairment), are expected to benefit most from mitral intervention. While subcategorization may help to inform treatment, there are no data on post-MI patients in this respect. Purpose To determine the incidence of discordant & concordant IMR categorised on echocardiography post-MI and impact on outcomes. Methods 1000 consecutive patients admitted to our hospital with myocardial infarction who underwent coronary angioplasty were included. Early inpatient TTE was performed by accredited echocardiographers using standard multiparametric quantification. Using TTE parameters, 4 subgroups were identified (figure) according to the degree of MR relative to LV remodelling. Thresholds were based on European guidelines (± 2SD from normal) and median value among survivors for vena contracta (VC): – LVEF: 52% (♂), 54% (♀) – Indexed LV end diastolic volume (LVEDVi): 74ml/m2 (♂), 61ml/m2 (♀) – Effective regurgitant orifice area (EROA) ≥0.2cm2 – Regurgitant volume (RVol) ≥30ml – VC ≥0.5cm Results MR was seen in 294/1000 patients (29.4%) with a severity of mild (76%), moderate (21%) and severe (3%). Concordant and discordant IMR were each seen in 16/294 (5%) of IMR patients post-MI. After a mean follow up of 3.2 years, IMR patients had a 3% rate of heart failure (HF) within 1 year and 19% mortality. Non-survivors had significantly worse IMR (PISA 0.65±0.25cm vs 0.54±0.19cm; p=0.033; VC 0.63±0.25cm vs 0.49±0.18cm; p=0.014), worse LV function (LVEF 44±17% vs 51±13%; p Conclusion 1) Significant predictors of mortality in IMR include LA dilatation and decline in LVEF, but not LV dilatation. 2) Although discordant severe IMR is uncommon following MI, mortality if left untreated remains high. Attention should be paid to early selection of this cohort for intervention. Funding Acknowledgement Type of funding source: None

Learning objectives Valvular heart disease (VHD) affects 1 in 50 of the general population and 1 in 3 of the over 65s, and is associated with increased morbidity and premature mortality.1 Among adults presenting to hospital with severe VHD, mitral regurgitation (MR: 21.3%) is the second and aortic regurgitation (AR: 5.3%) is the third most common valve lesion after aortic stenosis (41.2%).2 The predominance of MR above AR is also found in community-based studies, although it is much more common to find mild and moderate VHDs than severe disease in the general population.1 VHD of all types is more common with advancing age, and given the steady rise of life expectancy in the Western world, the frequency of patients presenting with MR and AR is increasing. Despite clear evidence of benefit from surgery when performed in a timely fashion, many patients undergo operation late in the course of disease, with more advanced symptoms and higher rates of heart failure and ventricular dysfunction.2 There is a long latent period in the majority of patients with either MR or AR, and timely diagnosis, careful monitoring and early referral remain critical to care. The severity of regurgitation through the MV and AV is governed by the Gorlin formula, which states that flow through an orifice varies by the square root of the pressure gradient across the orifice, the duration of flow and a discharge coefficient.3 Therefore, the main determinants …

Background Ischaemic mitral regurgitation (IMR) is associated with left atrial (LA) dilatation. In patients with primary MR, LA enlargement is an independent predictor of mortality following medical management and mitral valve surgery. The prognostic significance of LA dilatation in IMR post-myocardial infarction (MI) has not been studied. Purpose To determine the impact of LA dilatation on mortality in patients with IMR. Methods 1000 consecutive patients admitted to the Queen Elizabeth Hospital Birmingham with MI who underwent percutaneous coronary intervention were included. Early inpatient TTE was performed within 24-48 hours by accredited echocardiographers using standard multiparametric quantification of IMR, including proximal isovelocity surface area (PISA), effective regurgitant orifice (EROA), vena contracta (VC), and regurgitant volume (RVol). LA size was measured by the recommended biplane method for calculation of LA volume and indexed to body surface area (Mosteller). Analysis was performed on patients with indexed LA volume (LAVi) above and below 34ml/m2 (defined as the upper limit of normal in European Cardiovascular Imaging guidelines). Results MR was observed in 294/1000 patients (29.4%) post-MI, graded as mild (76%), moderate (21%) and severe (3%). A total of 275/294 (94%) had complete chamber volume data. LA dilatation (LAVi > 34ml/m2) was seen in 124 (45%) patients while 151/275 (55%) had normal LA volume (LAVi Although patients with LAVi > 34ml/m2 were older (76+/-11 years vs 70+/-12; p 34ml/m2 accounted for 60% of this mortality. Conclusion IMR patients with LA dilatation have significantly higher mortality than those with normal LA volume. Those with LAVi > 34ml/m2 account for 60% of all IMR mortality, despite fewer ST elevation infarcts and smaller troponin rise. Future studies of intervention for IMR should consider LA dilatation as a potential marker of outcome. Conflict of Interest None

Introduction Patients with repaired tetralogy of Fallot (RTOF) develop chronic pulmonary regurgitation and require monitoring for right ventricular dilatation. Pulmonary valve replacement can prevent irreversible right ventricular (RV) dilatation and dysfunction and cardiac magnetic resonance (CMR) is used to facilitate its optimal timing. There are however, different techniques published for measuring RV volumes. We sought to determine whether the choice of myocardial contouring technique affects preoperative RV volumetric thresholds for intervention. Methods Consecutive patients (n = 24, age 25.2±15.5 years, 42% male) with RTOF were identified retrospectively, having undergone CMR for clinical surveillance at a Level 1 ACHD surgical referral centre. Volumetric analysis was made by two experienced, independent observers blinded to clinical status. Right ventricular volumes were measured using three contouring techniques: 1) smooth, where the trabeculae were counted as part of the blood volume; 2) detailed, using semi-automated thresholding; 3) detailed, with manual contours. For 2) and 3), trabeculae and sub-valvar apparatus were counted as part of the myocardium. Inter-observer variability (F.L. & C.M.) was assessed blinded in 5 randomly selected patients. Results Right ventricular end-diastolic volume (EDV) was largest for smooth contours compared with thresholding and manual (table), as was end-systolic volume (ESV) (p Conclusions Smooth right ventricular contouring in RTOF creates larger RV volumes than detailed and may result in differences in management strategy. Smooth contouring is more reproducible than detailed methods using thresholding. Manual contouring was the least reproducible in this series. Our results are similar to studies of left ventricular contouring demonstrating larger volumes using smooth compared with detailed methods. The difference in right ventricular volume is accentuated in RTOF due to increased RV trabeculation. Consensus on contouring techniques in RTOF is vital to ensure standardisation of care. Conflict of Interest None

Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson’s biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e’). Results 160 patients (median age 75 years (IQR 69-82); 46% female) were included, with median heart rate 100 beats/min (IQR 86-112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Conflict of Interest Nothing to declare

Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 6-9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were collected from 86 patients with median CVF of 14.6%[IQR 7.4-20.3]. Fibrosis was present even in NYHA Class I patients (13.6%[6.3-18.8]), and was significantly higher than the 3.3%[2.6-6.1] obtained from 8 autopsy controls without cardiac disease (P Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although CVF did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV correlated with systolic (LVEF Rho=-0.22, P=0.029; LVESVi Rho 0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e’ R=0.25, P=0.022), exercise capacity (%VO2max R=-0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Following surgery, although LVEF remained >50% in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Conflict of Interest None

Background The inverse association between estimated glomerular filtration rate (eGFR) and cardiovascular risk is well recognised but not fully explained. Kidney donation is known to reduce renal function by approximately 30% and allows the prospective study of the cardiovascular effects of a reduced eGFR in healthy subjects without confounding comorbidities. We report five year results in a group of kidney donors and healthy controls who underwent extensive cardiovascular assessment. Methods A 5 year longitudinal, parallel group, blinded end-point study of living kidney donors (n=50) and healthy controls (n=45). Participants underwent office and 24-hr ambulatory blood pressure measures, multi-parametric cardiac magnetic resonance imaging (MRI) (3 Tesla), measurement of arterial stiffness (SphygmoCor), carotid intima-media thickness and blood and urine analysis at baseline, one year and 5 years from donation. Results The eGFR in donors at baseline was 95 ± 15ml/min/1.73m2, 65 ± 13ml/min/1.73m2 at one year and 67 ± 14ml/min/1.73m2 at 5 years. Left ventricular (LV) mass was 112g at baseline in both groups and was not different at 5 years (113 ± 31 vs. 115 ± 30, p=0.707). There was also no difference in LV volumes, LV geometry, LV function, T1 times or extracellular volume (ECV) on MRI. Office and ambulatory blood pressures did not differ from controls at any time point. Pulse wave velocity was higher in donors at one year but not significantly different by 5 years. At 5 years, there was no significant differences in the prevalence of a detectable troponin or mean plasma NT pro-BNP. Conclusion The stable reduction in eGFR to levels of 60-70 ml/min/1.73m2 after live kidney donation does not lead to deleterious changes in cardiovascular structure and function or biomarkers of cardiovascular disease at 5 years. Factors associated with kidney disease other than an isolated fall in eGFR are likely to explain the increased cardiovascular risk in patients with chronic kidney disease. Figure A and B: Longitudinal change in LV mass and PWV before and after donation in donors and controls. Black solid lines are means with confidence intervals for donors and dashed lines represent controls. Black squares indicate study visits. A; Left ventricular mass (g) and B; Adjusted pulse wave velocity (m/s) (adjusted for mean arterial pressure and heart rate). Conflict of Interest None

Background Carcinoid heart disease (CHD) develops as a complication of neuroendocrine tumours (NET). The prognosis of CHD without intervention is poor; 3 year survival is estimated at 31%. Surgical valve replacement is the only treatment for CHD, but is associated with a high 30-day mortality (10-15%) and prolonged recovery. Aim To identify pre-operative transthoracic echocardiogram (PTTE) findings that could determine which patients have a high likelihood of post-surgical mortality at 1 year. Methods This retrospective observational cohort study recruited 88 patients with a confirmed diagnosis of CHD between 2005-19 at University Hospital Birmingham; 49 (56%) of these were treated surgically. Indications for surgery were: stable NET, symptomatic severe valvular dysfunction, progressive RV dilatation or RV dysfunction, absence of significant comorbidities. Surgery was not offered to those patients that were unlikely to benefit, either due to frailty or short life expectancy, or if the disease severity which did not warrant surgical intervention. Patient demographics are reported in Table 1. All patients underwent a standard PTTE. PTTE parameters assessed included: right ventricular (RV) size, RV function (qualitative), TAPSE, RV fractional area change, RV S wave velocity, left ventricular (LV) size, LV ejection fraction and valvular velocities. Surgery was performed by a single surgical team using bioprosthetic valve replacements. Across the patient population there were 48 tricuspid, 39 pulmonary, six aortic and four mitral replacements. Five patients also underwent a coronary bypass graft procedure; 12 had a patent foramen ovale closure and 23 required implantation of a permanent pacemaker. Results Patients were followed up for a median of 15 months (IQR: 6-59) after surgery, during which time there were 33 deaths, giving a median survival time of 30 months (IQR: 7-85). Increasingly severe RV dilatation was significantly associated with shorter survival (p=0.032). The estimated survival rate at three years was 67% in those with normal RV size, compared to 24% in the severe RV group (Figure 1). RV basal diameter was then further assessed. ROC curve analysis for the outcome of one year survival returned an area under the curve of 0.66 (SE=0.10). Youden’s index identified RV diameter >4.8cm to be the optimal cut-off for identifying high-risk patients. One year mortality rates were 26% (7/27) vs. 75% (9/12) in those with RV basal diameter of ≤4.8 vs. >4.8cm (p=0.006). Conclusion A pre-operative right ventricular basal diameter >4.8cm is associated with a near three-fold increase in post-operative mortality at one year. These findings highlight the importance of regular imaging in order to optimise the timing of surgery in patients with CHD. Conflict of Interest None

Introduction Coronary microvascular dysfunction (CMD) is prevalent in chronic kidney disease (CKD), and may cause diffuse myocardial ischaemia and fibrosis, thus contributing to the elevated cardiac risk seen in CKD. Coronary flow reserve (CFR) is a marker of coronary microvascular function and can be measured using Doppler transthoracic echocardiography (TTE). Multiple studies have shown a graded inverse relationship between CFR and CKD stage, and this has prognostic significance. Living kidney donors (LKD) provide a population of subjects with reduced estimated glomerular filtration rate (eGFR), without the confounding cardiovascular risk factors usually associated with CKD. This provides an opportunity to study the effects of an isolated reduction in eGFR (which is usually in the range of CKD stage 2-3) on CFR. Methods 23 LKD and 25 controls of similar age and gender were studied. Individuals with diabetes, uncontrolled hypertension or ischaemic heart disease were excluded. All LKD were >12 months post donation. Subjects underwent adenosine stress TTE, myocardial contrast echocardiography (MCE) and CFR assessment. Peak diastolic coronary flow velocity (CFV) was measured in the distal left anterior descending artery at rest and at maximal hyperaemia (figure 1). CFR was calculated as the ratio of hyperaemic CFV/rest CFV. Results Controls and LKD were of similar age, gender and ethnicity (table 1). Rates of hypertension, smoking and hypercholesterolaemia were similar between the groups. Serum phosphate was significantly lower and detectable C reactive peptide was significantly higher in LKD. Left ventricular mass index and indices of systolic and diastolic function were similar between the two groups (table 2). No subjects had wall motion abnormalities on stress TTE or perfusion defects on MCE. CFR data was available in 22 controls and 23 LKD. CFR was significantly reduced in LKD compared to controls (mean CFR 3.8±0.6 vs 3.4±0.7, mean difference 0.4 95%CI 0.03-0.8, p=0.036) – figure 2. 6/23 (26%) LKD had CFR ≤2.7 (the lowest CFR value in controls.) Conclusions This is the first study of CFR in LKD. Similar to data in CKD, we have shown that a modest drop in eGFR is associated with reduced CFR in asymptomatic LKD. This suggests that isolated reductions in renal function may contribute to altered microvascular function, even in the absence of progressive CKD or cardiovascular risk factors. The higher prevalence of detectable CRP in LKD suggests that chronic inflammation may play a role in this process and this effect appears to persist even beyond the initial peri-operative period (median time from donation in LKD was 30 months). Reassuringly, no LKD had CFR These early microvascular changes highlight the importance of long term follow up and aggressive risk factor management in LKD, to minimise any future cardiac risk. They also shed light on the pathophysiology of myocardial disease in CKD. Further work is needed to elucidate the mechanisms of microvascular dysfunction in LKD and CKD. Conflict of Interest None

Background Ischaemic mitral regurgitation (IMR) confers a poor prognosis. Transcatheter mitral edge-to-edge repair may improve outcomes but MITRA-FR and COAPT trials have produced conflicting results, attributed to different patient selection criteria. Following acute myocardial infarction (MI), the number of patients eligible for transcatheter mitral repair using MITRA-FR and COAPT eligibility criteria is not known, nor whether these criteria produce cohorts with significantly different characteristics. Purpose To determine the number and characteristics of IMR patients qualifying for MITRA-FR and COAPT echocardiographic eligibility criteria amongst patients receiving coronary revascularization following acute MI. Methods 1000 consecutive patients admitted to the Queen Elizabeth Hospital Birmingham with acute MI who underwent coronary angioplasty were included. Early inpatient TTE was performed by accredited echocardiographers using standard multiparametric quantification, including (where possible) proximal isovelocity surface area (PISA), effective regurgitant orfice area (EROA), vena contracta (VC) regurgitant volume (RVol), regurgitant fraction (RF) and left ventricular ejection fraction (LVEF). Patients within our admission population fulfilling the following echo criteria were identified: MITRA-FR: LVEF 15-40% and EROA > 0.2cm2 or RVol > 30ml COAPT: LVEF 20-50% and either: Tier 1: EROA > 0.3cm2 or pulmonary vein flow reversal Tier 2: EROA > 0.2cm2 and 45ml/beat;RF > 40%;VC > 0.5cm; Tier 3: EROA 2 of the following:RVol > 45ml/beat;RF > 40%;VC > 0.5cm;PISA > 0.9cm but continuous wave of MR jet not done;Large (> 6cm) holosystolic jet wrapping around left atrium;Peak E wave velocity > 150cm/s. Results MR was observed in 294/1000 patients (29.4%) post-MI, graded as mild (76%), moderate (21%) and severe (3%). Based on MR characteristics alone (not including LVEF), the number of patients fulfilling MITRA-FR and COAPT eligibility criteria were 23 (7.8% of all IMR) and 24 (8.1% of all IMR) respectively. Both groups had a similar ratio of moderate:severe MR (74:26% vs 75:25%), EROA (0.34+/-0.13cm2 vs 0.35+/-0.13cm2), VC (0.6+/-0.2cm vs 0.6+/-0.2cm), RVol (52+/-24ml vs 51+/-25ml), indexed LA volume (LAVi) (54+/-20ml/m2 vs 51+/-20ml/m2), indexed LV end-diastolic volume (LVEDVi) (62+/-17ml/m2 vs 63+/-18ml/m2), LVEF (48+/-13% vs 47+/-13%) and mortality (MITRA-FR: 23% vs COAPT: 29%, p=0.9243). After including LVEF as a criterion, the number of patients eligible for MITRA-FR and COAPT were just 5 (1.7% of all IMR) and 14 (4.7% of all IMR) respectively. As expected, COAPT patients had a higher mean LVEF (MITRA-FR: 33% vs COAPT: 40%; p=0.077). Both groups remained similar with respect to ratio of moderate:severe MR (60:40% vs 64:36%), EROA (0.40+/-0.13 vs 0.38+/-0.15cm2), VC (0.6+/-0.2cm vs 0.6+/-0.2cm), LAVi (56+/-20ml/m2 vs 50+/-19ml/m2), LVEDVi (69+/-25ml/m2 vs 67+/-19ml/m2) and mortality (MITRA-FR: 40% vs COAPT: 35%). Conclusion Post-acute MI, more patients with IMR met COAPT criteria (4.7%) than MITRA-FR echocardiographic criteria (1.7%) however both cohorts had similarly high mortality. Notwithstanding the difference in LVEF, MITRA-FR and COAPT echo criteria identified almost identical cohorts post-MI. Conflict of Interest None

Background Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacement fibrosis and diffuse myocardial fibrosis (DIF). The pathogenesis of heart failure is thought to involve fibroblast accumulation and expansion of the extracellular matrix with excess protein deposition, leading to distorted organ architecture and impaired contractile function. Consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease in Birmingham, England were studied. All patients underwent serial CMR, echocardiography and venous blood sampling, with computed tomography coronary angiography (CTCA) performed to assess severity of CAD. The aims of this study were: 1) to evaluate changes over time in DIF by cardiovascular magnetic resonance tissue characterization in ALMS; 2) to examine whether changes in DIF are associated with alteration in systolic or diastolic function; and 3) to evaluate the frequency and severity of coronary artery disease as a confounder for progression of ischaemic versus non-ischaemic fibrosis. Results In total, 30/32 adults (63% male; 67% White British) participated. The median age at first scan was 21.3 years (interquartile range: 19.0–32.6) and participants were followed for a maximum of 67 months. Only 4 patients had significant coronary artery stenosis on post-mortem, invasive coronary angiography or CTCA. Mid short axis myocardial T1 times, myocardial extracellular volume, and left ventricular mass increased significantly over time, by an average of 21.8 ms (95% CI 17.4–26.1; p p 2 (1.9–3.7; p Conclusions This is the first comprehensive prospective study demonstrating progression of DIF in ALMS over time, although no structural or functional consequences were noted within a median three and a half years’ follow up. Further study is warranted to define whether DIF is a by-stander or the driver to impaired contractile function, heart failure and death.

Secondary mitral regurgitation (sMR) is characterized by left ventricular (LV) dilatation or dysfunction, resulting in failure of mitral leaflet coaptation. sMR complicates up to 35% of ischaemic cardiomyopathies (1) and 57% of dilated cardiomyopathies (2). Due to the prevalence of coronary artery disease worldwide, ischaemic cardiomyopathy is the most frequently encountered cause of sMR in clinical practice. Although mortality from cardiovascular disease has gradually fallen in Western countries, severe sMR remains an independent predictor of mortality (3) and hospitalization for heart failure (4). The presence of even mild sMR following acute MI reduces long-term survival free of major adverse events (1). Such adverse outcomes worsen as the severity of sMR increases, due to a cycle in which LV remodeling begets sMR and vice versa. Current guidelines do not recommend invasive treatment of the sMR alone as a first-line approach, due to the paucity of evidence supporting improvement in clinical outcomes. Furthermore, a lack of international consensus on the thresholds that define severe sMR has resulted in confusion amongst clinicians determining whether intervention is warranted (5, 6). The recent Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial (7) assessing the effectiveness of transcatheter mitral valve repair is the first study to demonstrate mortality benefit from correction of sMR and has reignited interest in identifying patients who would benefit from mitral valve intervention. Multimodality imaging, including echocardiography and cardiovascular magnetic resonance (CMR), plays a key role in helping to diagnose, quantify, monitor, and risk stratify patients for surgical and transcatheter mitral valve interventions.

Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor‐23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor‐23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end‐stage renal disease.