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Background Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. Methods We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. Results Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P  = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P  = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P  = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79–15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81–7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24–5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. Conclusions LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.

Aims Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium‐glucose co‐transporter‐2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR‐Reduced trial and cardiovascular mortality in the EMPA‐REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR). Methods and results The EMPA‐VISION trial is a double‐blind, randomized, placebo‐controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine‐to‐adenosine triphosphate ratio, as measured by 31Phosphorus‐MRS. Conclusions EMPA‐VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR‐Reduced and EMPEROR‐Preserved).

The British Society of Heart Failure (BSH) meetings highlight the latest advancements within the field of heart failure (HF) and provide education for training and revalidation for cardiologists and general physicians. This article reviews take-home messages from the 7th BSH HF revalidation and training meeting. It emphasises what every physician needs to know about the latest acute HF guidelines, diagnostics in HF, management strategies (including pharmacotherapeutics and device therapy), and when to consider referring to a transplant centre for mechanical circulatory support or transplantation. It describes the practical challenges faced and provides clinicians with a framework to assist with service development and commissioning of resources to deliver optimal, integrated services that meet the ever-advancing needs of our HF communities.

Doc number: T1

Despite significant progress in cardiovascular pharmacotherapy and interventional strategies, cardiovascular disease (CVD), in particular ischaemic heart disease, remains the leading cause of morbidity and mortality among women in the UK and worldwide. Women are underdiagnosed, undertreated and under-represented in clinical trials directed at management strategies for CVD, making their results less applicable to this subset. Women have additional sex-specific risk factors that put them at higher risk of future cardiovascular events. Psychosocial risk factors, socioeconomic deprivation and environmental factors have an augmented impact on women’s cardiovascular health, highlighting the need for a holistic approach to care that considers risk factors specifically related to female biology alongside the traditional risk factors. Importantly, in the UK, even in the context of a National Health Service, there exist significant regional variations in age-standardised mortality rates among patients with CVD. Given most CVDs are preventable, concerted efforts are necessary to address the unmet needs and ensure parity of care for women with CVD. The present consensus document, put together by the British Cardiovascular Society (BCS)’s affiliated societies, specifically portrays the current status on the sex-related differences in the diagnosis and treatment of each of the major CVD areas and proposes strategies to overcome the barriers in accessing diagnoses and treatments among women. This document aims at raising awareness of the scale of the current problem and hopes to stimulate a multifaceted approach to address sex disparities and enable future comprehensive sex- and gender-based research through collaboration across different affiliated societies within the BCS.

Despite significant progress in cardiovascular pharmacotherapy and interventional strategies, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality among females in the UK and worldwide. This might be due to lack of robust evidence in the best care of females with CVD related to under-representation of females in clinical trials (females accounting for <30% of trial participants). Recently, the British Cardiovascular Society (BCS), together with the affiliated societies, put together a consensus document specifically describing the current status on the sex differences in each of the major disease areas and proposed strategies/actionable points to overcome the barriers in access to diagnosis and treatment of CVD among females.In order to address the disparities, several research organisations, including the UK National Institute for Health and Care Research (NIHR), have produced guidance to diversify research participation and representation. The UK government has developed a Women’s Health Strategy for England. In the present consensus, we evaluate the barriers to research participation of female participants across the CVD spectrum and describe specific strategies/actionable points to enhance female involvement in clinical cardiovascular research. It is hoped that this document will stimulate a multifaceted approach to address disparities, including raising awareness and undertaking sex/gender-based research. We aim to improve the current status of management in various disease areas among females by collaboration across different affiliations within the BCS, the British Heart Foundation Clinical Research Collaborative and the NIHR to collectively work towards improving the health and well-being of females with CVD.

BackgroundDilated cardiomyopathy (DCM) is the leading cause of non-ischaemic heart failure. It causes approximately 10,000 deaths in Europe per year. Studies suggest that up to 50% of patients with DCM have a genetic predisposition and that mutations within one of 40 genes coding for structural and functional cardiac proteins accounts for up to 40% of familial disease. The relevance of genotype to clinical phenotype, treatment and prognosis is poorly understood. This study aimed to clinically and genetically characterise probands with familial DCM using next-generation sequencing technology (NGS) to determine specific genotype-phenotype correlations in DCM.Methods72 probands with DCM were consecutively recruited into this study within our centre. All received pre-test genetic counselling and provided written informed consent. All patients were clinically characterised using a standard phenotyping protocol. Genomic data isolated from peripheral blood lymphocytes using standardised protocols, was collected and screened for all major genes involved in cardiomyopathies and selected candidate genes using NGS. Eighty-six genes with 1528 exons representing 500kb of coding sequence, were studied using target enrichment methods (Agilent SureSelect System) followed by sequencing on the Illumina HiSeq 2000 platform. Clinical parameters were correlated with genotype findings.ResultsVariant calling from 72 probands (male 54%, age 41 years (mean 40.7, range 14 to 68 years) generated 1415 exonic and splice-site calls. After filtering, 420 distinct candidate variants were reported, 253 of which were published pathogenic mutations, 112 of which were frameshift insertion/deletion or splice-site variants predicted to cause loss of function (thus likely to be pathogenic). A further 55 novel variants were considered potentially pathogenic on the basis of preliminary in silico analysis. Each proband, on average, carried 3 published pathogenic variants which included known mutations associated with DCM and other forms of cardiomyopathy. Up to two further variants predicted to be pathogenic were identified per DCM proband illustrating genetic heterogeneity. However, there was no simple correlation between a specific mutation or the number of mutations and the clinical phenotype. Moreover, there was no evidence of a ‘poly-hit’ theory of multiple mutations contributing to a worsened phenotype nor of specific variant demonstrating causality of phenotype suggesting that genotype-phenotype correlations in DCM are complex and may be influenced by both genetic and epigenetic factors.ConclusionThis study demonstrates the exciting potential for utilisation of next generation sequencing in routine clinical practice. However it highlights the genetic heterogeneity and high frequency of novel variants with uncertain effects on gene function in DCM. This presents considerable challenges for clinical interpretation. Large-scale phenotyping is therefore required to fully understand genotype-phenotype relations in DCM.

BackgroundPositron emission tomography (PET) performed utilising the glucose analogue and radiotracer 18F-FDG (FDG) to detect active inflammation, offers enormous potential for detecting disease presence and activity in myocarditis. However, the clinical utility of PET imaging is limited by the unpredictable nature of physiological FDG uptake within cardiac muscle. Methods to minimise physiological FDG uptake are necessary to depict active inflammation and to avoid avoid false negative and positive findings. Studies have suggested the use of fasting conditions to shift myocardial metabolism to primary free fatty acid (FFA) utilisation for energy and oxygen consumption to suppress physiological FDG uptake by normal myocardium. Specific dietary preparation regimens using a very high-fat content and low-carbohydrate diet prior to scanning have also been proposed, as has the administration of heparin to reduce FDG uptake through the activation of lipoprotein lipase (LPL) and hepatic lipase (HL) which enhances plasma lipolytic activity and leads to preferential free fatty acid consumption.This study was therefore performed to develop an optimal dietary preparation protocol for imaging in PET/CT. We sought to establish whether patient preparation using heparin in addition to a high fat, low carbohydrate diet and prolonged fast prior to scanning ncreases the diagnostic capability of PET scanning in myocarditis.MethodsAll patients referred for PET scans for the assessment of myocarditis were enrolled. We prospectively examined three preparation rationales to determine the optimal rationale for minimising physiological FDG-uptake. All subjects underwent strict preparation prior to scanning using one of the following protocols to enable comparison:A 6-hour fast only, no dietary preparation.Dietary preparation for 24 h prior to the scan with a high-fat content, low carbohydrate diet, followed by a prolonged fast for 12 h.Dietary preparation for 24 h prior to the scan with a high-fat content, low carbohydrate diet, followed by a prolonged fast for 12 h and the administration of 50IU/kg of heparin prior to scanning.The imaging findings were analysed by two independent and blinded clinicians. FDG uptake was categorised as none (complete suppression, no uptake = 0), focal (localised uptake, = 1), focal on diffuse (2) and diffuse (poor, failed suppression, = 4).ResultsA total of 280 PET scans were performed. 36 patients underwent preparation using a 6-hour fast only, 128 underwent dietary preparation and a 12-hour fast, and 118 underwent dietary preparation followed by a 12-hour fast and the administration of heparin prior to scanning.A 6-hour fast alone was associated with a 44% failure to suppress physiological metabolism – equivalent to almost one in every two scans being suboptimal or un-interpretable. In contrast, restriction of carbohydrate intake with high fat intake alongside a prolonged 12-hour fast was successful in supressing normal myocardial metabolism in 89% of subjects. Similarly, of those who also received heparin, there was a failure to suppress normal myocardial metabolism in 11% of subjects.ConclusionStrict patient preparation prior to PET scanning is key to ensuring an optimal diagnostic disease assessment in myocarditis. A short duration of fasting of 6-hours or less alone is suboptimal in suppressing physiological uptake. In contrast, strict dietary preparation (using a high fat, low carbohydrate diet) and prolonged fast of > 12 h increases the diagnostic capability by 75%. Interestingly, the addition of heparin to this regimen provided no additive benefit suggesting that the addition of heparin adds little to the diagnostic quality of scans and is therefore unnecessary.

IntroductionMyocardial perfusion scintigraphy (MPS) is one of the most commonly performed non-invasive imaging procedures for the diagnosis of Coronary Artery Disease (CAD). Two large trials evaluating over 21,000 patients with a normal SPECT study have demonstrated the safety of stress-only imaging as compared to traditional stress/rest imaging. Comparably low all-cause and cardiac mortality rates were observed with both imaging protocols. This was true irrespective of patient age, gender, cardiac risk factor profile, or stressor employed with SPECT. These results are consistent with earlier studies evaluating patient outcome following normal stress-only imaging. The best use of a stress-only imaging strategy is likely to be in the selected low or intermediate risk population, which forms the referral basis for myocardial perfusion imaging. In this study, we describe the introduction of stress only MPS in comparison to traditional stress/rest MPS.Old PathwayThe traditional stress/rest MPS pathway requires two imaging sessions either the same day or on two separate days according to the patient’s Body Mass Index (BMI). For a 1 day protocol typically the injected activity is split in a 1:3 ratio between the first and second injections. For BMI <30, a total of 1125 MBq is administered. For BMI 30–35, a total of 1475 MBq is administered. For BMI>35, a total of 2000 MBq is administered 1:1. If the BMI is not provided by the requesting clinician then a letter is sent to the patient asking their height and weight.New PathwayFrom September 2014 through December 2014, we introduced selective stress only imaging. A single high dose MIBI stress dose of of 800 MBq, was authorised for all patients, regardless of BMI. After stress imaging, a decision was made regarding the necessity of rest imaging.ResultsPatients were referred from 10 hospitals. 407 patients were scanned. 55% were male and 45% female. Their average age was 66 years (+/-12.9). Their average BMI was 29.4 kg/m2 (+/-6.4).Of the total, 35% percent were normal at stress imaging and did not have rest imaging. Of the 65% who were abnormal, 60% of the combined rest/stress scans were interpreted as abnormal. As a result of this, the average time from request to appointment date for the stress scan reduced from 27 to 14 days.The average time between stress scan and rest scan was 2.5 (range: 1–21 days). The average report turn around time from request to report for MPS was 5 days, but 97% of normal stress only scans were reported the same day. Furthermore, the administered radiation dose was lower for 67% of all patients.In additional to scanning parameters being assessed, patients preferences were also assessed via a questionnaire. 49% expressed a preference for the test to be split across 2 days. 7% said either 1 day or 2 days. 20% of patients had to take a day off work to attend the hospital.ConclusionStress only MPS reduces radiation exposure, increases efficiency and thereby reduces cost.