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Apnea (breath-holding) elicits co-activation of sympathetic and parasympathetic nervous systems, affecting cardiac control. In situations of autonomic co-activation (e.g., cold water immersion), cardiac arrhythmias are observed during apnea. Chronic endurance training reduces resting heart rate in part via elevation in parasympathetic tone, and has been identified as a risk factor for development of arrhythmias. However, few studies have investigated autonomic control of the heart in trained athletes during stress. Therefore, we determined whether heightened vagal tone resulting from endurance training promotes a higher incidence of arrhythmia during apnea. We assessed the heart rate, rhythm (ECG lead II), and cardiac inotropic (speckle-tracking echocardiography) response to apnea in 10 endurance trained and 7 untrained participants. Participants performed an apnea at rest and following sympathetic activation using post-exercise circulatory occlusion (PECO). All apneas were performed prior to control (CON) and following vagal block using glycopyrrolate (GLY). Trained participants had lower heart rates at rest ( p = 0.03) and during apneas ( p = 0.009) under CON. At rest, 3 trained participants exhibited instances of junctional rhythm and 4 trained participants developed ectopy during CON apneas, whereas 3 untrained participants developed ectopic beats only with concurrent sympathetic activation (PECO). Following GLY, no arrhythmias were noted in either group. Vagal block also revealed increased cardiac chronotropy (heart rate) and inotropy (strain rate) during apnea, demonstrating a greater sympathetic influence in the absence of parasympathetic drive. Our results highlight that endurance athletes may be more susceptible to ectopy via elevated vagal tone, whereas untrained participants may only develop ectopy through autonomic conflict.

Sashiananthan Ganesananthan,1,2 Abeer Zahid,2 Anam Choudhry,2 Thivya V Vadiveloo,2 Nailah Khan,2 Ting Yang,2 Haroon Urrehman,2 Sahana Mahesh,2 Zaheer Yousef2– 4 1National Heart and Lung Institute, Imperial College London, London, UK; 2Cardiff University School of Medicine, Cardiff University, Cardiff, Wales, UK; 3Department of Cardiology, University Hospital Wales, Cardiff, Wales, UK; 4Welsh Heart Research Institute, Cardiff University, Cardiff, Wales, UKCorrespondence: Sashiananthan Ganesananthan, National Heart and Lung Institute, Imperial College London, London, UK, Email sashiganes96@yahoo.co.ukIntroduction: Conferences are an important avenue for dissemination of knowledge, research and provide networking opportunities for career development. The COVID-19 pandemic has prompted adoption of virtual platforms for delivery of these conferences. The aim of the study was to determine the utility and educational impact of a student-led virtual webinar to deliver an undergraduate cardiovascular conference compared to a traditional in-person conference.Methods: We conducted a two-day virtual conference using the Zoom platform in June 2021. The conference consisted of cardiology subspecialty lectures, and workshops were conducted by a junior doctor, senior cardiology trainees and consultants. The conference also outlaid a virtual poster hall and oral presentation session while networking opportunities were encouraged using breakout rooms and poster hall chat function. A 38-item self-administered online questionnaire was designed and disseminated at the end of the conference to all attending delegates. All data analysis and data visualisation strategies were conducted on R statistical programming.Results: Eight-hundred and forty students from 55 countries attended the event. Four hundred and ninety participants (58.5% response rate, 55.9% female) completed the questionnaire. Factors such as weekend conference (84.9%), student-led or organised (84.1%), environmental/sustainable (82.3%), appropriate level for me (81.5%) and comfort to present (80.8%) were deemed to be at least equal to traditional in-person conference. The conference also increased participants’ interest, their core cardiology knowledge and improved their critical analysis and basic echocardiography skills [median 4 (IQR 3– 5) for all parameters]. Overall, participants also found it easy to use the virtual platform [median 5 (IQR 5– 5)] and easier to ask questions compared to in-person conferences [median 5 (IQR 4– 5) vs median 4 (IQR 3– 5), p < 0.001].Conclusion: Our virtual conference provided opportunities to students that the COVID-19 pandemic would have otherwise affected; however, its utility and educational impact will need to be assessed within its individual context of delivery.Keywords: virtual conference, undergraduate, international, educational impact, cardiology, webinar

BackgroundAcute coronary syndrome (ACS) is caused by arterial thrombosis and is associated with sustained activation of coagulation. Clotting requires interactions of coagulation factors with aminophospholipids (aPL): phosphatidylserine (PS) and phosphatidylethanolamine (PE) on membrane surfaces. The aPL composition of circulating membranes in coronary disease has not been characterized. Furthermore, the contribution of external-facing aPL to elevated thrombotic risk in ACS is unknown.Methods and resultsThrombin generation was measured on platelet, leukocyte and extracellular vesicles (EV) from patients with ACS (n = 24), stable coronary artery disease (CAD, n = 18), risk factor positive (RF, n = 23) and healthy controls (HC, n = 24). The aPL composition on the surface of EV, platelets and leukocytes was determined using lipidomics. Leukocytes, platelets and EV externalized PE- and PS-containing fatty acids ranging from C16:0-20:4. These included both diacyl and plasmalogen forms, with significant increases stimulated by agonist activation. Thrombin generation on the surface of EV and leukocytes was higher in ACS than HC. Also, thrombin generation was higher for EV from CAD and RF, than HC. EV counts were higher in CAD and ACS compared with HC. Thrombin generation correlated positively with plasma EV counts and membrane surface area.ConclusionThe aPL membrane of EV and leukocytes may contribute to the activation of coagulation in CAD and ACS. Targeting EV formation/clearance and the aPL surface of EV and leukocyte membranes represents a novel anti-thrombotic target in CAD and ACS.Condensed abstractAcute coronary syndrome (ACS) is associated with sustained activation of coagulation, requiring procoagulant aminophospholipids (aPL). However, the aPL composition of circulating membranes and their contribution to thrombotic risk in ACS is undetermined. Lipidomics demonstrated that leukocytes, platelets and extracellular vesicles (EV) externalized aPL-containing fatty acids ranging from C16:0-20:4. Thrombin generation on the surface of EV and leukocytes was higher in ACS patients than healthy controls (HC). EV counts were higher in ACS compared with HC and correlated positively with thrombin generation. In summary, aPL in the outer membranes of EV and leukocytes may contribute to elevated thrombotic risk in ACS.HighlightsWhat is new?The aPL profile of platelets, leukocytes and EV in patients with ACS, CAD, RF and HC is defined for the first-time using lipidomics.Thrombin generation on the surface of unstimulated leukocytes, is elevated in patients with ACS compared with HC.Thrombin generation on the surface of EV is elevated in patients with ACS, CAD and RF compared with HC.EV counts in patients with ACS/CAD/RF were elevated compared with HC and correlate positively with thrombin generation.Clinical PerspectiveWhat are the clinical implications?The membranes of EV and leukocytes may contribute to the activation of coagulation in ACS.The aPL in EV and leukocyte membranes represent a novel target for reducing thrombotic risk in ACS.Targeting EV formation/clearance could reduce thrombotic risk in CAD and ACS.

Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world’s population. Over time, CKD can cause renal dysfunction and progression to end-stage kidney disease and cardiovascular disease. Complications associated with CKD may contribute to the acceleration of disease progression and the risk of cardiovascular-related morbidities. Early CKD is asymptomatic, and symptoms only present at later stages when complications of the disease arise, such as a decline in kidney function and the presence of other comorbidities associated with the disease. In advanced stages of the disease, when kidney function is significantly impaired, patients can only be treated with dialysis or a transplant. With limited treatment options available, an increasing prevalence of both the elderly population and comorbidities associated with the disease, the prevalence of CKD is set to rise. This review discusses the current challenges and the unmet patient need in CKD.

Enzymatically oxygenated phospholipids (eoxPL) formed by lipoxygenases (LOX) and cyclooxygenase (COX) in platelets and leukocytes are pro-coagulant in multiple model systems. However, their generation in arterial thrombotic disease, and how their levels are modulated by common therapies is unknown. Here, eoxPL were first characterized in isolated platelets and leukocytes from an arterial vascular disease cohort, a healthy cohort administered low dose aspirin, and from retrieved human arterial thrombi. In both cohorts, aspirin reduced platelet COX-1-derived eoxPL, while elevating diacyl 12-LOX-derived eoxPL in males, through enhanced Lands’ cycle esterification. Conversely, P2Y12 inhibition reduced 12-LOX-derived eoxPL in leukocytes. Complex aspirin-dependent gender and seasonal effects on platelet eoxPL were seen in healthy subjects. Limb or coronary (STEMI) thrombi showed a platelet eoxPL signature while carotid thrombi had a white cell profile. Mice genetically lacking leukocyte 12/15-LOX, which are deficient in eoxPL, generated smaller carotid thrombi in vivo. In summary, pro-coagulant eoxPL generation is altered in human arterial vascular disease by commonly used cardiovascular therapies. These changes to the phospholipid composition of blood cells in humans at risk of thrombotic events may be clinically significant where the pro-coagulant membrane plays a central but poorly understood role in driving elevated thrombotic risk.Key PointseoxPL generation is altered in health and arterial vascular disease by aspirin or P2Y12 inhibitors, and shows gender and seasonal variation.Aspirin regulates eoxPL by inhibiting cyclooxygenase and modulating Lands’ cycle.The eoxPL profile of human arterial thrombi identifies platelet and leukocyte involvement.Mice deficient in LOX-derived eoxPL form smaller arterial thrombiin vivo.

Background Temporary cardiac pacing, conventionally achieved using a passive transvenous pacing wire, can be life-saving for unstable arrhythmias. However, they run the risk of complications, the longer they remain in-situ. Externalized prolonged temporary pacing (EPTP), using active-fixation lead and an externalized pulse generator; may be an alternative for transient pacing indications, concurrent illness or sepsis that precludes permanent pacing. Methods Sixty-seven patients (mean age 69 ± 14 years; 82% male) underwent EPTP between November 2011 and April 2019. EPTP was performed in a sterile facility, under fluoroscopy, using active-fixation leads anchored to the right ventricle septum. Externalized lead was connected to a re-sterilized pulse generator and secured to anterior chest wall with transparent dressings. EPTP indications and patient outcomes were evaluated. Results Pacing indications were high-grade atrio-ventricular (AV) block (73.2%), sinus arrest (14.9%), overdrive suppression of VT (5.9%) and pause-dependent VT (4.5%). Reasons for ETPT rather than permanent pacing included: sepsis (38.8%), CIED-related infection (8.9%), transient pacing indication (25%), to allow further investigations prior to decision on CIED type (22%), and over-drive arrhythmia suppression (6%). Sixty three percent patients were severely ill in an ICU. Mean duration of pacing was 16 ± 12 days. Sixty seven percent patients subsequently received a CIED and had no evidence of device-related infection at 1-year post-implant. There were three non-fatal complications during EPTP while no deaths were attributed to EPTP. Conclusion EPTP is a safe and useful method of prolonged temporary pacing for patients who require chronotropic support, but in whom immediate permanent pacemaker implantation is contraindicated.

Early diagnosis and effective management of type 2 diabetes (T2D) are crucial in reducing the risk of developing life-changing complications such as heart failure, stroke, kidney disease, blindness and amputation, which are also associated with significant costs for healthcare providers. However, as T2D symptoms often develop slowly it is not uncommon for people to live with T2D for years without being aware of their condition—commonly known as the undiagnosed missing million. By the time a diagnosis is received, many individuals will have already developed serious complications. While the existence of undiagnosed diabetes has long been recognised, wide-reaching awareness among the general public, clinicians and policymakers is lacking, and there is uncertainty in how best to identify high-risk individuals. In this article we have used consensus expert opinion alongside the available evidence, to provide support for the diabetes healthcare community regarding risk prediction of the missing million. Its purpose is to provide awareness of the risk factors for identifying individuals at high, moderate and low risk of T2D and T2D-related complications. The awareness of risk predictors, particularly in primary care, is important, so that appropriate steps can be taken to reduce the clinical and economic burden of T2D and its complications.

Left ventricular (LV) structural remodeling following athletic training has been evidenced through training-specific changes in wall thickness and geometry. Whether the LV response to changes in hemodynamic load also adapts in a training-specific manner is unknown. Using echocardiography, we examined LV responses of endurance-trained (

A 46-year-old South Asian male with no comorbidity presented with palpitations and presyncope. There was no history of chest pain, and no family history of premature atherosclerosis, cardiomyopathy or sudden death. The presenting ECG is shown in figure 1A. Routine blood tests, including full blood count and inflammatory markers, were unremarkable. Admission troponin I was elevated at 470 ng/L (normal 0–34 ng/L), peaking at 1450 ng/L. Serum angiotensin-converting enzyme was marginally elevated at 63 U/L (normal 8–52 U/L). Echocardiography demonstrated normal biventricular dimensions, with moderate biventricular systolic impairment. Invasive angiography revealed unobstructed coronary arteries. Cardiac magnetic resonance (CMR) imaging demonstrated marked hypokinesia of the interventricular septum and right ventricular outflow tract free …

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are among the most effective drugs for treating people with type 2 diabetes (T2D), they are clinically under-utilised. Until recently, the only route for semaglutide administration was via subcutaneous injection. However, an oral formulation of semaglutide was recently licensed, with the potential to address therapy inertia and increase patient adherence to treatment, which is essential in controlling blood glucose and reducing complications. The availability of oral semaglutide provides a new option for both clinicians and patients who are reluctant to use an injectable agent. This has been of particular importance in addressing the challenge of virtual diabetes care during the COVID-19 pandemic, circumventing the logistical problems that are often associated with subcutaneous medication administration. However, there remains limited awareness of the clinical and economic value of oral semaglutide in routine clinical practice. In this article, we present our consensus opinion on the role of oral semaglutide in routine clinical practice and discuss its value in reducing the burden of delivering diabetes care in the post-COVID-19 pandemic period of chronic disease management.

ObjectiveWe provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in theDMD-gene.MethodsInitiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD.ResultsThe resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivanet aland are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society.ConclusionThese guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.

NEW FINDINGS What is the central question of this study? Endurance athletes demonstrate altered regional right ventricular (RV) wall mechanics, characterized by lower basal deformation, in comparison to non-athletic control subjects at rest. We hypothesized that regional adaptations at the RV base reflect an enhanced functional reserve capacity in response to haemodynamic volume loading. What is the main finding and its importance? Free wall RV longitudinal strain is elevated in response to acute volume loading in both endurance athletes and control subjects. However, the RV basal segment longitudinal strain response to acute volume infusion is greater in endurance athletes. Our findings suggest that training-induced cardiac remodelling might involve region-specific adaptation in the RV functional response to volume manipulation. ABSTRACT Eccentric remodelling of the right ventricle (RV) in response to increased blood volume and repetitive haemodynamic load during endurance exercise is well established. Structural remodelling is accompanied by decreased deformation at the base of the RV free wall, which might reflect an enhanced functional reserve capacity in response to haemodynamic perturbation. Therefore, in this study we examined the impact of acute blood volume expansion on RV wall mechanics in 16 young endurance-trained men (aged 24 ± 3 years) and 13 non-athletic male control subjects (aged 27 ± 5 years). Conventional echocardiographic parameters and the longitudinal strain and strain rate were quantified at the basal and apical levels of the RV free wall. Measurements were obtained at rest and after 7 ml/kg i.v. Gelofusine infusion, with and without a passive leg raise. After infusion, blood volume increased by 12 ± 4 and 14 ± 5% in endurance-trained individuals versus control subjects, respectively (P = 0.264). Both endurance-trained individuals (8 ± 10%) and control subjects (7 ± 9%) experienced an increase in free wall strain from baseline, which was also similar following leg raise (7 ± 10 and 6 ± 10%, respectively; P = 0.464). However, infusion evoked a greater increase in basal longitudinal strain in endurance-trained versus control subjects (16 ± 14 vs. 6 ± 11%; P = 0.048), which persisted after leg raise (16 ± 18 vs. 3 ± 11%; P = 0.032). Apical longitudinal strain and RV free wall strain rates were not different between groups and remained unchanged after infusion across all segments. Endurance training results in a greater contribution of longitudinal myocardial deformation at the base of the RV in response to a haemodynamic volume challenge, which might reflect a greater region-specific functional reserve capacity.

The prevalence of type 2 diabetes continues to increase, along with a proliferation of glucose-lowering treatment options. There is universal agreement in the clinical community for the use of metformin as the first-line glucose-lowering therapy for the majority of patients. However, controversy exists regarding the choice of second-line therapy once metformin is no longer effective. The most recent treatment consensus focuses on the presence of cardiovascular disease, heart failure or kidney disease as a determinant of therapy choice. The majority of patients in routine practice, however, do not fall into such categories. Heart failure and kidney disease represent significant clinical and cost considerations in patients with type 2 diabetes and have a close pathophysiological association. Recent data has illustrated that sodium-glucose transporter 2 (SGLT2) inhibitor therapy can reduce the burden of heart failure and the progression of renal disease across a wide range of patients including those with and without established disease, supported by an increased understanding of the mechanistic effects of these agents. Furthermore, there is growing evidence to illustrate the overall safety profile of this class of agents and support the benefit-risk profile of SGLT2 inhibitors as a preferred option following metformin monotherapy failure, with respect to both kidney disease progression and heart failure outcomes.

ObjectivesHeart failure (HF) is a prevalent condition associated with poor quality-of-life and high symptom burden. As patients reach ceilings of survival-extending interventions, their priorities may be more readily addressed through the support of palliative care services; however, the best model of care remains unestablished.We aimed to create and evaluate a cospeciality cross-boundary service model for patients with HF that better provides for their palliative care needs in the latter stages of life, while delivering a more cost-effective patient journey.MethodsIn 2016, the Heart Failure Supportive Care Service (HFSCS) was established to provide patient-centred holistic support to patients with advanced HF. Patient experience questionnaires were developed and distributed in mid-2018 and end-of-2020. Indexed hospital admission data (in-patient bed days pre-referral/post-referral) were used allowing statistical comparisons by paired t-tests.ResultsFrom 2016–2020, 236 patients were referred to the HFSCS. Overall, 75/118 questionnaires were returned. Patients felt that the HFSCS delivered compassionate care (84%) that improved symptoms and quality of life (80% and 65%). Introduction of the HFSCS resulted in a reduction in HF-related admissions: actual days 18.3 to 4 days (pConclusionThis service demonstrates that a cospeciality cross-boundary method of care delivery successfully provides the benefits of palliative care to patients with HF in a value-based manner, while meeting the priorities of care that matter to patients most.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first developed as glucose-lowering therapies for the treatment of diabetes. However, these drugs have now been recognised to prevent worsening heart-failure events, improve health-related quality of life, and reduce mortality in people with heart failure with reduced ejection fraction (HFrEF), including those both with and without diabetes. Despite robust clinical trial data demonstrating favourable outcomes with SGLT2 inhibitors for patients with HFrEF, there is a lack of familiarity with the HF indication for these drugs, which have been the remit of diabetologists to date. In this article we use consensus expert opinion alongside the available evidence and label indication to provide support for the healthcare community treating people with HF regarding positioning of SGLT2 inhibitors within the treatment pathway. By highlighting appropriate prescribing and practical considerations, we hope to encourage greater, and safe, use of SGLT2 inhibitors in this population.

Objective: Revision to cardiac resynchronisation therapy (CRT) in patients with existing pacemakers with worsening heart failure (HF) can improve symptoms and cardiac function. We identify factors that predict improvement in left ventricular ejection fraction (LVEF) within a year of CRT revision. Methods: We performed a retrospective study of 146 consecutive patients (16% female, mean age 73 ± 11 years, mean LVEF 27 ± 8%) undergoing revision to CRT (January 2012 to May 2018) in a single tertiary centre. LVEF was measured pre-revision and 3, 6 and 12 months post-upgrade. Results: At 6 months, 68% of patients demonstrated improvement in LVEF (mean ΔLVEF + 6.7% ± 9.6). Compared to patients in atrial fibrillation (AF), patients with sinus rhythm had a greater improvement in LVEF at 6 months (sinus 8.4 ± 10.3% vs. AF 4.2 ± 8.0%, p = 0.02). Compared to ischaemic cardiomyopathy (ICM), patients with non-ischaemic cardiomyopathy (NICM) had a greater improvement in LVEF at 6 months (NICM 8.4 ± 9.8% vs ICM 4.8 ± 9.2%, p = 0.05). Patients with RV pacing ≥40% at baseline had a greater improvement in LVEF at 6 months (≥40% RV pacing 9.3 ± 10.2 vs.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway. Mullens, W (corresponding author), Ziekenhuis Oost Limburg, Dept Cardiol, Schiepse Bos 6, B-3600 Genk, Belgium. wilfried.mullens@zol.be

Background: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. Methods: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II–III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2–4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. Findings: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (−36 mm Hg, 95% CI −43·2 to −28·1; p2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB −1·8, −2·4 to −1·2; p

Metal-on-metal (MOM) hip prostheses have a higher failure rate than conventional prostheses and leaching of cobalt and chromium has been linked to cardiomyopathy. We screened MOM subjects to evaluate if cobalt and chromium are related to subclinical cardiac dysfunction.A single centre, non-randomised, observational study using echocardiography in 95 patients who had undergone MOM hip prostheses, and 15 age matched controls with non-MOM hip replacement. Serial plasma cobalt and chromium levels were recorded, and data compared by tertiles of cobalt exposure.Indexed left ventricular (LV) end-diastolic and end-systolic volumes (EDVi and ESVi) increased with tertile of cobalt (omnibus p = 0.003 for EDVi and ESVi), as did indexed left atrial (LA) volumes (p = 0.003). MOM subjects had 25% larger EDVi than controls, 32% larger ESVi (40 ml vs. 32 ml, and 15 ml vs. 11 ml, p = 0.003 for both) and 28% larger indexed LA (23 ml vs. 18 ml, p = 0.002). There were no differences in LV systolic or diastolic function, including ejection fraction, tissue velocity and mitral E/e'. Estimated glomerular filtration rate was 18% lower in the highest tertile compared with the lowest (p = 0.01) and correlated inversely with LA volume (r = -0.36, p 0.001) and LV EDV (r = -0.24, p = 0.02).No correlations between sensitive measures of systolic or diastolic cardiac function or serum cobalt/chromium levels were observed in this study. However, there was a relationship between increasing left ventricular and left atrial volumes and declining renal function with high cobalt levels which requires further evaluation in MOM patients.

Introduction The hallmark of Heart Failure with Preserved Ejection Fraction (HFpEF) is exercise intolerance. The mechanisms for this are numerous, but chronotropic incompetence, defined as a failure to reach at least 70% of the age-predicted maximum heart rate (HR) on maximal exercise, has been reported to contribute. Impaired Heart Rate Reserve, a measure of HR achieved on maximal exercise compared with age-predicted maximum heart rate, is correlated with negative cardiovascular outcomes. In normal subjects, the PR interval shortens during exercise as parasympathetic tone reduces. This is known as dromotropy and is reduced in subjects with coronary artery disease. We formed the hypothesis that HFpEF patients may also have impaired PR shortening and that this may contribute to exercise intolerance. Methods and results HFpEF patients and controls (healthy (H), hypertensive (HT) and breathless controls (BC)) from the MEDIA (Metabolic Road to Diastolic Heart Failure, EU FP7) trial at our centre underwent maximal semi-supine bicycle stress tests whilst on standard treatment. Electrocardiograms were examined by a single, blinded investigator for PR-interval and heart rate (HR) at: rest; submaximal exercise (HR 100 min-1); peak exercise; and 2 and 5 min after exercise. 110 subjects were recruited, of whom 24 were excluded (unable to exercise/atrial arrhythmia). Data on 86 subjects were analysed. Baseline characteristics are given in the Table. Resting HR was similar between groups, but maximal HR was lower in patients than all controls (p Patients were 13% older than controls (p Conclusions Patients with HFpEF have chronotropic incompetence and impaired HR recovery, but there was no evidence of dromotropic incompetence in this study.

BackgroundSacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables.Methods and resultsFrom June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration. Clinical assessment, biochemistry, echocardiography and QoL were compared pretreatment and post-treatment switching. We were able to successfully switch 89% of patients from renin–angiotensin axis inhibitors to sacubitril/valsartan (71 of 80 patients). After 3 months of switch therapy, we observed clinically significant and incremental improvements in blood pressure (systolic blood pressure 123 vs 112 mm Hg, pConclusionThis study provides real-world clinical practice data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan. The data provide evidence beyond that observed in clinical trial settings of the potential benefits of sacubitril/valsartan when used as part of a multidisciplinary heart failure programme.

Pacemaker therapy is inaccessible to most patients with bradycardia in Africa. Use of reconditioned pacemakers has been proposed as a safe, efficacious, and ethical means of delivering this therapy. A collaboration between PASCAR, Pace4Life, and Project My Heart Your Heart is working to address this deficit in health care in Africa.

BACKGROUND: Reports on the incidence and causes of sudden cardiac death among young athletes have relied largely on estimated rates of participation and varied methods of reporting. We sought to investigate the incidence and causes of sudden cardiac death among adolescent soccer players in the United Kingdom. METHODS: From 1996 through 2016, we screened 11,168 adolescent athletes with a mean (±SD) age of 16.4±1.2 years (95% of whom were male) in the English Football Association (FA) cardiac screening program, which consisted of a health questionnaire, physical examination, electrocardiography, and echocardiography. The FA registry was interrogated to identify sudden cardiac deaths, which were confirmed with autopsy reports. RESULTS: During screening, 42 athletes (0.38%) were found to have cardiac disorders that are associated with sudden cardiac death. A further 225 athletes (2%) with congenital or valvular abnormalities were identified. After screening, there were 23 deaths from any cause, of which 8 (35%) were sudden deaths attributed to cardiac disease. Cardiomyopathy accounted for 7 of 8 sudden cardiac deaths (88%). Six athletes (75%) with sudden cardiac death had had normal cardiac screening results. The mean time between screening and sudden cardiac death was 6.8 years. On the basis of a total of 118,351 person-years, the incidence of sudden cardiac death among previously screened adolescent soccer players was 1 per 14,794 person-years (6.8 per 100,000 athletes). CONCLUSIONS: Diseases that are associated with sudden cardiac death were identified in 0.38% of adolescent soccer players in a cohort that underwent cardiovascular screening. The incidence of sudden cardiac death was 1 per 14,794 person-years, or 6.8 per 100,000 athletes; most of these deaths were due to cardiomyopathies that had not been detected on screening. (Funded by the English Football Association and others.).

Inherited cardiac conditions comprise many different structural and cardiac rhythm abnormalities. Many are asymptomatic and can be detected as an incidental finding or during routine medical screening and require pedigree evaluation, risk stratification, and ongoing long-term surveillance. Structural inherited cardiac conditions (ICC) can cause heart failure with primary heart muscle defects, impaired ventricular function, pump failure or sudden cardiac death. The arrhythmic ICC can present with a range of arrhythmias as a result of different channalopathies and notably brady and tachy arrhythmias and sudden cardiac death (SCD).

Objectives The effects of acute coronary syndrome (ACS) events on health-related quality-of-life (HRQoL) and the time dependency of these effects are unknown. This study aimed to characterize health utilities in ACS patients to aid development of future economic models estimating the cost per quality-adjusted life-year impact of ACS events and potential treatments. Methods Multi-center, non-interventional, longitudinal evaluation of health utility in patients experiencing ACS or stroke events. EuroQol-5 dimension 3 level (EQ-5D-3L) surveys were sent to patients (≥18 years) from three UK centers, 1 month after hospital discharge for myocardial infarction (MI), unstable angina (UA), or stroke. Patient demographics, lifestyle, and baseline utility score were collected in the first survey. Follow-up surveys were sent at 6, 12, 18, and 24 months to prospectively capture utility and subsequent health events. Two methods of patient identification were adopted-prospective, where the patient's qualifying events occurred after the study index date, and retrospective, where the patient's qualifying event occurred prior to the study index date. General healthy population utility values were assumed for pre-event HRQoL. Results Between January 2011 and March 2014, 2,103 prospectively (n = 1,350)/retrospectively (n = 753) identified patients (mean age = 68.3 years; 67.9% male) responded: MI = 55.9% (n = 1,176), UA = 42.7% (n = 898), stroke = 1.4% (n = 29); 24% had type 2 diabetes. Post-event utility values were lower than general healthy population values, although significant differences in utility between subsequent 6 (n = 1,031, change = -0.002), 12 (n = 1,096, change = -0.008), 18 (n = 1,246, change = -0.007), and 24 (n = 1,277, change = -0.004) month timepoints were not detected. Through multivariate regression analyses, wheelchair use, current smoking, and secondary mental and joint health events were associated with the greatest statistically significant utility decrements. Conclusions This study indicates that health utility decreases following a cardiovascular event and, although some improvement occurs over the subsequent 24 months, general healthy population utility is not necessarily attained.

Aims To provide comprehensive information on the access and use of cardiac implantable electronic devices (CIED) and catheter ablation procedures in Africa. Methods and results The Pan-African Society of Cardiology (PASCAR) collected data on invasive management of cardiac arrhythmias from 2011 to 2016 from 31 African countries. A specific template was completed by physicians, and additional information obtained from industry. Information on health care systems, demographics, economics, procedure rates, and specific training programs was collected. Considerable heterogeneity in the access to arrhythmia care was observed across Africa. Eight of the 31 countries surveyed (26%) did not perform pacemaker implantations. The median pacemaker implantation rate was 2.66 per million population per country (range: 0.14–233 per million population). Implantable cardioverter-defibrillator and cardiac resynchronization therapy were performed in 12/31 (39%) and 15/31 (48%) countries respectively, mostly by visiting teams. Electrophysiological studies, including complex catheter ablations were performed in all countries from Maghreb, but only one sub-Saharan African country (South Africa). Marked variation in cost (up to 1000-fold) was observed across countries with an inverse correlation between implant rates and the procedure fees standardized to the gross domestic product per capita. Lack of economic resources and facilities, high cost of procedures, deficiency of trained physicians, and non-existent fellowship programs were the main drivers of under-utilization of interventional cardiac arrhythmia care. Conclusion There is limited access to CIED and ablation procedures in Africa. A quarter of countries did not have pacemaker implantation services, and catheter ablations were only available in one country in sub-Saharan Africa.

Aims: The number of patients with cardiac implantable electronic devices (permanent pacemakers and implantable cardioverter defibrillators) undergoing radiotherapy treatment is increasing. The aims of this audit were to establish current UK practice regarding the management of patients with implanted cardiac devices undergoing radiotherapy and to compare this practice with current ‘gold standard’ evidence-based guidelines. Materials and methods: All UK radiotherapy departments were contacted and asked to provide their current cardiac implantable electronic device policy or to indicate if there was no current policy. A proforma was created to analyse these polices and to compare with current best practice. Results: In total, 47/67 (70%) radiotherapy departments responded and 45 departmental policies were submitted; 31/45 (69%) policies defined the radiotherapy tolerance dose to permanent pacemakers and 14/45 (31%) defined the monitoring procedure for patients in line with current best practice. Only 5/45 (11%) policies defined the radiotherapy tolerance dose to implantable cardioverter defibrillators and 12/45 (27%) defined the monitoring procedure in line with current best practice. Conclusion: Most UK cardiac device policies do not reflect current best evidence. Policies are based on research carried out in 1994 by the American Association of Physicists in Medicine. This evidence does not account for advances in cardiac implantable electronic device technology. Further research is urgently needed to establish the effect of radiotherapy on these devices.

BackgroundCurrently there exists no widely accepted, objective tool for determining the probability of shock in the emergency department (ED). Associated mortality outcomes remain unacceptably high. Using variables that are associated with shock and available in the ED we aimed to derive an objective tool for estimating the probability of shockMethodsIn a prospective, longitudinal study conducted in the ED, Cardiff, adult patients aged ≥18 years, presenting with NEWS ≥3 were recruited. We derived a model consisting of 8 variables, and validated it using bootstrap (1000 iterations; random number seed: 978). The primary outcome was combined 30-day mortality or ICU admission.Results361 patients were recruited (mean age 69.4 ±15.9 years; male 62.7%; 80 positive outcome) to the study. The multivariate model variables were: Glasgow Coma Scale 3–8 (Odds ratio (OR) 9.1 (95% CI 1.2–69.4) p=0.0324), 9–12 (OR 1.3 (95% CI 0.4–4.2) p=0.6561); capillary return >4 (OR 8.7, (95% CI 2.9–26.1) p=0.0001), 3–4 (OR 3.7 (95% CI 1.3–10.4); p=0.0113); temperature ≤35°C (OR 5.4, (95% CI 1.8–16.3); p=0.0045); bilirubin >34 (OR 4.9, (95% CI 1.6–14.5); p=0.0045); oxygen supplement (OR 1.9, (95% CI 1.0–3.7); p=0.06); respiratory rate >24 (OR 2.6, (95% CI 1.3–5.1); p=0.0069); and albumin The model was a 100-point scale where 0 was low probability and 100 was maximal probability of shock. The AUC was 0.801 (95% CI 0.756–0.841), accuracy 82%, p35, and Youden Index 0.4557 the sensitivity and specificity were 56.2% (95% CI 44.7–67.3) and 89.32% (95% CI 85.1–92.7) respectively. At a fixed specificity of 80%, the estimated sensitivity was 60.5% (95% CI 49.4–71.3). At a fixed sensitivity of 80%, the estimated specificity was 62.3% (95% CI 45.9–71.2).ConclusionsAn accurate 7-point ED tool for shock has been derived and internally validated.

Introduction\ud The re-purposing of the anti-anginal drug perhexiline (PHX) has resulted in symptomatic improvements in heart failure (HF) patients. The inhibition of carnitine palmitoyltransferase-1 (CPT-1) has been proposed as the primary mechanism underlying the therapeutic benefit of PHX. This hypothesis is contentious. \ud \ud Areas covered\ud We reviewed the primary literature and patent landscape of PHX from its initial development in the 1960s through to its emergence as a drug beneficial for HF. We focused on its physico-chemistry, molecular targets, tissue accumulation and clinical dosing. \ud \ud Expert opinion\ud Dogma that the beneficial effects of PHX are due primarily to potent myocardial CPT-1 inhibition is not supported by the literature and all available evidence point to it being extremely unlikely that the major effects of PHX occur via this mechanism. In vivo PHX is much more likely to be an inhibitor of surface membrane ion channels and also to have effects on other components of cellular metabolism and reactive oxygen species (ROS) generation across the cardiovascular system. However, the possibility that minor effects of PHX on CPT-1 underpin disproportionately large effects on myocardial function cannot be entirely excluded, especially given the massive accumulation of the drug in heart tissue.

OBJECTIVES: Optimized temporary bi-ventricular (BiV) pacing may benefit heart failure patients after on-pump cardiac surgery compared with conventional dual-chamber right ventricular (RV) pacing. An improvement in haemodynamic function with BiV pacing may reduce the duration of ‘Level 3’ intensive care. METHODS: Thirty-eight patients in sinus rhythm, ejection fraction ≤35%, undergoing on-pump surgical revascularization, valve surgery or both were enrolled in this study. Before closing the sternum, temporary epicardial pacing wires were attached to the right atrium, RV outflow tract and basal posterolateral wall of the left ventricle. Patients were randomly assigned to postoperative BiV pacing with the optimization of the atrio- (AV) and inter-ventricular (VV) pacing intervals (Group 1) or conventional dual-chamber right AV pacing (Group 2). The primary end-point was the duration of ‘Level 3’ intensive care. Secondary end-points included cardiac output which was measured by thermodiluation at admission to the intensive care unit and at 6 and 18 h later, in five different pacing modes. RESULTS: The duration of ‘Level 3’ care was similar between groups (40 ± 35 vs 54 ± 63 h; Group 1 vs 2; P= 0.43). Cardiac output was similar in all pacing modes at baseline. At 18 h, cardiac output with BiV pacing (5.8 l/min) was 7% higher than atrial inhibited (5.4 l/min) and 9% higher than dual-chamber RV pacing (5.3 l/min; P= 0.02 and 0.001, respectively). Optimization of the VV interval produced a further 4% increase in cardiac output compared with baseline settings (P= 0.005). CONCLUSIONS: Postoperative haemodynamic function may be enhanced by temporary BiV pacing of high-risk patients after on-pump cardiac surgery.

Introduction Over 1 million metal-on-metal (MOM) hip replacements were performed between 2003 and 2010. These prostheses were intended to be more durable than previous models, but have been associated with a higher failure rate. There have also been isolated cases of fulminant cardiomyopathy in patients with very high serum cobalt levels. We screened a cohort of asymptomatic patients with these prostheses for subclinical cardiac abnormalities. Methods All patients with MOM hip replacements at our centre undergo regular follow-up in the orthopaedic clinic with serum cobalt and chromium levels, and periodic magnetic resonance scanning of the affected joint. We recruited consecutive asymptomatic patients to receive echocardiography and recorded demographic data including age, height, weight, serum cobalt and chromium levels, and date of prosthesis implantation. Echocardiographers were blinded to medical history and laboratory results. The cohort was split into quartiles of serum cobalt. ANOVA, Kruksall-Wallis H test and Chi-squared tests were used to evaluate the differences between groups. Results Baseline characteristics between each quartile were similar (table 1). Mean duration of implant increased with quartile, but serum cobalt was not correlated with duration of prosthesis (r=0.135, p=0.162). Patients in the highest quartile of serum cobalt levels had larger left ventricular end-diastolic and end-systolic dimensions (50.8 vs. 44.7 mm, p=0.018; 31.6 vs. 25.8 mm, p=0.014 respectively) and indexed end-diastolic and end-systolic volumes by Simpsons method (42.0 vs. 32.8 ml/m2, p Conclusions Subjects with the highest serum cobalt levels have larger left ventricular and left atrial chamber sizes than those with the lowest serum levels. However, no difference in even sensitive markers of systolic or diastolic function were found. Left ventricular measurements are part of a range and therefore it is not possible to specify a cut-off for abnormality in these people. Whilst our findings do not suggest a clear relationship between serum ion levels and basic echocardiographic parameters of left ventricular systolic and diastolic dysfunction, we cannot exclude an idiosyncratic response as described in isolated case reports. We therefore advise that patients with MOM hip replacements undergo serial cardiology follow up.

Objectives To examine the evidence base for telemonitoring designed for patients who have chronic obstructive pulmonary disease and heart failure, and to assess whether telemonitoring fulfils the principles of monitoring and is ready for implementation into routine settings. Design Qualitative data collection using interviews and participation in a multi-path mapping process. Participants Twenty-six purposively selected informants completed semi-structured interviews and 24 individuals with expertise in the relevant clinical and informatics domains from academia, industry, policy and provider organizations and participated in a multi-path mapping workshop. Results The evidence base for the effectiveness of telemonitoring is weak and inconsistent, with insufficient cost-effectiveness studies. When considered against an accepted definition of monitoring, telemonitoring is found wanting. Telemonitoring has not been able so far to ensure that the technologies fit into the life world of the patient and into the clinical and organizational milieu of health service delivery systems. Conclusions To develop effective telemonitoring for patients with chronic disease, more attention needs to be given to agreeing the central aim of early detection and, to ensure potential implementation, engaging a wide range of stakeholders in the design process, especially patients and clinicians.

Despite the availability of potentially curative interventions for atrial fibrillation, there remains an important role for conventional anti-arrhythmic therapy and anti-coagulation combined with direct current cardioversion. Unfortunately, the latter approach is disturbed by high recurrence rates of atrial fibrillation. In recent years, several adjunctive therapies have emerged which may facilitate the maintenance of sinus rhythm. These novel therapies and their potential mechanisms of action are reviewed in this article.

Item does not contain fulltext OBJECTIVE: To propose a research agenda that addresses technological and other knowledge gaps in developing telemonitoring solutions for patients with chronic diseases, with particular focus on detecting deterioration early enough to intervene effectively. DESIGN: A mixed methods approach incorporating literature review, key informant, and focus group interviews to gain an in-depth, multidisciplinary understanding of current approaches, and a roadmapping process to synthesise a research agenda. RESULTS: Counter to intuition, the research agenda for early detection of deterioration in patients with chronic diseases is not only primarily about advances in sensor technology but also much more about the problems of clinical specification, translation, and interfacing. The ultimate aim of telemonitoring is not fully agreed between the actors (patients, clinicians, technologists, and service providers). This leads to unresolved issues such as: (1) How are sensors used by patients as part of daily routines? (2) What are the indicators of early deterioration and how might they be used to trigger alerts? (3) How should alerts lead to appropriate levels of responses across different agencies and sectors? CONCLUSION: Attempts to use telemonitoring to improve the care of patients with chronic diseases over the last two decades have so far failed to lead to systems that are embedded in routine clinical practice. Attempts at implementation have paid insufficient attention to understanding patient and clinical needs and the complex dynamics and accountabilities that arise at the level of service models. A suggested way ahead is to co-design technology and services collaboratively with all stakeholders.

Objective This study examines the relationship between heart rate recovery following exercise and subsequent response to cardiac resynchronisation therapy (CRT). Background Blunted heart rate recovery is an adverse prognostic marker in heart failure and has been shown to correlate with disease severity. Methods 37 patients receiving biventricular pacemakers for conventional indications underwent functional assessments; cardiopulmonary exercise test, 6-min walk test and quality-of-life assessment, together with echo analyses, before and at 3 months following implant. Heart rate deceleration (HRD) gradients were calculated at 30-, 60-, 90- and 120-s intervals following cessation of the baseline exercise test and compared with subsequent markers of response to CRT. Functional response was defined as ≥20% improvement in any two of the three functional assessments, and echo response defined as ≥5% increase in ejection fraction. Results Functional responders demonstrated steeper HRD gradients than non-responders at 30, 60 and 90 s. Echo responders also demonstrated steeper HRD at 30 and 60 s from the cessation of exercise. Receiver-operating curve analysis demonstrates area under the curve of 0.87 and 0.82, respectively, for HRD30 to predict functional and echo response to CRT. A cut-off value of 3 for HRD30, equating to a 5% reduction in HR between peak exercise and 30 s into recovery, demonstrates the optimal sensitivity/specificity profile to perform this function. Conclusions HRD following exercise correlates with functional and echocardiographic response to CRT. Application of this parameter in addition to standard criteria may provide valuable supplementary information in the evaluation of prospective CRT candidates.