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Introduction Positron Emission Tomography/Computed Tomography (PET/CT) has many advantages over Single Photon Emission Computed Tomography in Myocardial Perfusion Imaging (MPI). However, UK availability, has been limited. We describe a new Rubidium (Rb) PET MPI service; the third in the National Health Service in England. Methods Audit of the first 100 patients from November 2019 to January 2020. 66 men, 34 women, mean age 65 ±11, mean Body Mass Index 28.3 ±6.8. Imaging comprised CT for attenuation correction, CT for Agatston scoring if no known Coronary Artery Disease (CAD) or prior intervention, and PET with and without adenosine vasodilation. Results The commonest indication was symptoms post-revascularization (36%). 31% had had previous percutaneous intervention, 15% had had previous coronary surgery. 21% had had prior cardiac CT. The mean wait from request to scan was 30 days. 98% were reported the same or next working day. 96% received 140 mcg/kg/min adenosine, 4% received 210 mcg/kg/min. Two patients did not show adequate vasodilation. All PET MPI scans were diagnostic quality. 43% had Agatston scoring. The mean total Agatston score was 511. The normalcy rate for PET MPS was 60%. The prevalence of infarction was 20%. The mean Myocardial Flow Reserve was 2.3 ±0.8. Conclusion Rb PET MPI is feasible and high quality in a new service. It provides detailed coronary assessment, with plaque burden, relative perfusion and absolute myocardial blood flow quantification. It will be an essential contributor to patient diagnosis, treatment response and risk stratification.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

Acute cardiothoracic and respiratory diseases frequently remain a challenge to diagnose and differentiate in the emergency setting. The main diseases that manifest with chest pain include ischaemic heart disease, myocarditis, acute pericarditis, aortic dissection/rupture and pulmonary embolism (PE). Diseases that primarily present with dyspnoea include heart failure (HF), acute respiratory distress syndrome (ARDS), pneumonia, asthma exacerbations and chronic obstructive pulmonary disease. Pre-test probabilities of clinical findings play a vital part in diagnostic decisions, and the use of a Bayesian approach to these greatly improves the ability to stratify patients more accurately. However, blood tests (biomarkers) are increasingly used to assist in rapid decision-making in the emergency setting in combination with imaging methods such as chest radiograph, ultrasound and increasingly computed tomography, as well as physiological tests such as the electrocardiogram in addition to physical examination. Specific tests for ischaemic heart disease and myocarditis (cardiac troponins), HF (B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP)), aortic dissection (smooth muscle markers) and PE (D-dimer) have been developed. Surfactant protein-D and interleukin-8 have been developed for ARDS. Additionally, circulating microRNAs have emerged as promising biomarker candidates in cardiovascular disease. With this increasing array of biochemical markers to aid in the diagnosis of chest diseases presenting with chest pain and dyspnoea, we herein review the clinical usefulness of these markers, in particular in differentiating cardiac from pulmonary diseases. A symptom-oriented assessment as necessary for use in the critical setting is described in addition to discussion of individual biomarkers.

Gene therapy has been applied to cardiovascular disease for over 20 years but it is the application to heart failure that has generated recent interest in clinical trials. There is laboratory and early clinical evidence that delivery of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy is beneficial for heart failure and this therapy could become the first positive inotrope with anti-arrhythmic properties. In this review we will discuss the rationale for SERCA2a gene therapy as a viable strategy in heart failure, review the published data, and discuss the ongoing clinical trials, before concluding with comments on the future challenges and potential for this therapy.

Aims There are few non-invasive techniques to predict and monitor patients' responses to left ventricular assist device (LVAD) therapy. MicroRNAs (miRs) are small non-coding RNAs with intricate roles in cardiovascular disease. They are stable in the circulation, readily quantified, and may be useful as new biomarkers. This study sought to identify candidate miR biomarkers for further investigation. Methods and results We studied 53 plasma and 20 myocardial samples from 19 patients who underwent HeartMate II LVAD implantation, and used a screening microarray to analyse the change in expression of 1113 miRs after 6 months LVAD support. Twelve miRs showed significant variation and underwent validation, yielding miR-1202 and miR-483-3p as candidate biomarkers. In the test cohort, circulating miR-483-3p showed early and sustained up-regulation with LVAD support, with median (interquartile range) fold changes from baseline of 2.17 (1.43–2.62; P = 0.011), 2.27 (1.12–2.42; P = 0.036), 1.87 (1.64–4.36; P = 0.028), and 2.82 (0.70–10.62; P = 0.249) at 3, 6, 9, and 12 months, respectively, whilst baseline plasma miR-1202 identified good vs. poor LVAD responders [absolute expression 1.296 (1.293–1.306) vs. 1.311 (1.310–1.318) arbitrary units; P = 0.004]. Both miRs are enriched in ventricular myocardium, suggesting the heart as the possible source of the plasma fraction. Conclusions This is the first report of circulating miR biomarkers in LVAD patients. We demonstrate the feasibility of this approach, report the potential for miR-483-3p and miR-1202, respectively, to monitor and predict response to LVAD therapy, and propose further work to study these hypotheses and elucidate roles for miR-483-3p and miR-1202 in clinical practice and in underlying biological processes.

Mechanical circulatory support forms a crucial and expanding element of advanced heart failure management. Short-term assistance is delivered in emergency situations or where the underlying condition is likely to quickly worsen, and these approaches are discussed in Chapter 30. This chapter focuses on implantable devices intended for the medium and long term. The first half of the chapter is aimed directly at practical clinical management, whilst the second half considers the evidence base for contemporary practice. The chapter concludes by considering new paradigms for implantable cardiac support. Most frequently, these devices support left ventricular function (left ventricular assist devices), and this comprises the majority of our discussion.

Takotsubo syndrome (TTS), also known as takotsubo cardiomyopathy, is an acute heart failure syndrome that typically occurs after a period of great emotional stress. The archetypal patient is a postmenopausal woman who presents with chest pain, ST-segment elevation and acute hypokinesia of the apical and middle segment of the left ventricle that extends beyond the territory of a single coronary artery, coupled with hyperkinesia of the basal myocardium. Recent preclinical and clinical studies have shown the importance of high catecholamine levels in precipitating TTS. We propose that this is caused by activation of β-adrenoceptors and the subsequent activation of a negatively-inotropic pathway, perhaps to protect the heart from catecholamine overload. We explore the pathophysiology of TTS according to its "phases", both preclinically and clinically. This will show that the condition is not one of static apical hypokinesia that simply improves, but rather a dynamic condition that changes as the disease progresses. We hope that further exploration of TTS using its "phases" will aid in its characterization, diagnosis and treatment.

s S235 level of SDF-1a at explant. CXCR4 expression remained unchanged following CF-LVAD support, however it tended to be lower in DM pts suggesting an impaired ability in endogenous stem cell mobilization. Conclusion: Chronic LVAD therapy down regulates SDF-1a expression likely as a consequence of effective unloading. DM pts exhibit the lowest levels of SDF-1a. Low SDF-1a expression may lead to impaired mobilization of endogenous stem cells and negatively affect myocardial recovery. Whether therapeutic SDF-1 administration in this setting could promote recovery should be further investigated.

Purpose There are few non-invasive techniques to predict and monitor patients’ responses to left ventricular assist device (LVAD) therapy. MicroRNAs (miRs) are small noncoding RNAs with intricate roles in cardiovascular disease. They remain stable in the circulation, are readily quantified, and may be useful as new biomarkers. This study sought to identify candidate miR biomarkers for further investigation and to investigate whether these circulating miRs were of myocardial origin. Methods and Results We studied 55 serial plasma and myocardial samples from 19 patients who underwent HeartMate II LVAD implantation, and used a screening microarray to analyse the change in expression of 1,113 miRs from pre-implant and 6 months follow-up. Twelve miRs showed significant variation and underwent validation, with miR-1202 and miR-483–3p selected for further study. The key findings in the test cohort (n = 8) were: (1) miR-483–3p showed upregulation after 6 months of LVAD therapy in circulating plasma (median fold change 2.32 (1.30–2.44); p = 0.021) and in ventricular myocardium (median fold change 1.799 (0.717–4.719; p = 0.169). This mirrored the reduction in NT-proBNP levels at 6 months (fold change 0.30 (0.08–0.43); p = 0.004; see Figure). (2) Using change in NT-proBNP at 3 months as a marker of clinical response to LVAD therapy, baseline expression of plasma miR-1202 identified good versus poor LVAD responders (absolute expression 1.296 (1.293–1.306) vs. 1.311 (1.310–1.318) A.U.; p = 0.004). (3) Both miR-483–3p and miR-1202 are also enriched in ventricular myocardium suggesting the heart as the possible source of these plasma miRs. Conclusions This is the first report of circulating miR biomarkers in LVAD patients. We demonstrate the feasibility of this approach, and report the potential for miR-483–3p and miR-1202 respectively to monitor and predict response to LVAD therapy. We suggest that changes in miR-483–3p expression could provide a more specific assessment of ventricular function that complements the changes in systemic neuroendocrine milieu recorded by serial measurement of natriuretic peptides, and suggest that miR-1202 could be valuable for judging the likelihood of good response to LVAD support. However, these conclusions are weakened by small sample size and retrospective analysis. We propose further work to study these hypotheses further and elucidate roles for miR-483–3p and miR-1202 in clinical practice and in underlying biological processes.

British Journal of Hospital Medicine, July 2013, Vol 74, No 7 415 © 2 01 3 M A H ea lth ca re L td found. However, currently this remains an extremely rare occurrence, and at this time we do not think the diagnostic criteria, including reversibility, should be amended. This question also underlines the need for complete national and international registries of takotsubo cardiomyopathy that will help to provide more information to help answer these exact questions. Andrew C Morley-Smith Clinical Research Fellow National Heart and Lung Institute Imperial College and National Institute for Health Research Cardiovascular Biomedical Research Unit Royal Brompton Hospital London SW3 6NP Elmir Omerovic Associate Professor of Cardiology Department of Molecular and Clinical Medicine Sahlgrenska Academy at University of Gothenburg Division of Cardiology Sahlgrenska University Hospital Gothenburg Sweden Alexander R Lyon Senior Lecturer and Consultant Cardiologist National Heart and Lung Institute Imperial College and National Institute for Health Research Cardiovascular Biomedical Research Unit Royal Brompton Hospital London