2014 BUCA Journal

Volume 2 Issue 2 Autumn 2014

1 Â www.bucardiology.org.uk

EDITORIAL TEAM Chief Lead ExecuHve Editor Mahvesh Rana Javaid Barts & The London

Journal Team Contributor Rachel Wamboldt Southampton Univerisity

Chief Editor Rafail Angelos Kotronias Keele University

Journal Team Contributor ShruK Jayakumar Keele University

Chief Editor Marilena Giannoudi Newcastle University

Journal Team Contributor KrisKana Geide Swansea University

Journal Design Mahvesh Rana Javaid Barts & The London

Abstracts System Technical Support Dil Hussain BriKsh Cardiovascular Society

REVIEWERS TEAM Dr Andrew Deaner Consultant Cardiologist, Barts Health NHS Trust

Mr Wael Awad Consultant Cardiothoracic Surgeon, Barts NHS Trust

Dr Duncan Dymond Consultant Cardiologist, Barts Health NHS Trust

Dr Mohammed Khanji Clinical Research Fellow & Cardiology Speciality Registrar, Barts & The London

Professor Steffen Petersen Consultant Cardiologist, Barts Health NHS Trust

Dr Filip Zemark Clinical Research Fellow & Cardiology Speciality Registrar, Barts & The London

Dr Dr Kulasegaram Ranjadayalan Consultant Cardiologist, Barts NHS Trust

Dr Afzal Shoaib Clinical Research Fellow & Cardiology Speciality Registrar, Imperial College London

2

CONTENTS 4

FOREWORD

5

OUR HISTORY

6

REVIEWS Health Economics In Cardiology Policy Decision-Making Kotronias RA

Cardiopulmonary Bypass and Acute Kidney Injury Jayakumar S Cardiac Screening in Athletes: High Profile With Big Barriers Wamboldt R

26 CARDIAC EDUCATION Diabetes Mellitus and Coronary Heart Disease Wamboldt R The Undergraduate Guide to Interpreting Angiograms Giannoudi M

30 CARDIAC CASE IMAGES Angiogram Giannoudi M

32 SUPPLEMENTS Oral Presentations O1-­‐O5

Poster Presentations P1-­‐P18

22 ELECTIVE REPORTS An Elective Report in Cardiology Datanni A

An Elective Report in Cardiac Surgery Giannoudi M

3

FOREWORD Since the summer of 2013, a subgroup of students within the Bri;sh Undergraduate Cardiovascular Associa;on (BUCA) have worked hard to launch and publish the Bri;sh Undergraduate Cardiovascular (BUC) Journal. In our second issue, this exci;ng ini;a;ve sets out to act as a reliable and up-­‐to-­‐date source of informa;on for undergraduate students and junior doctors with an interest in Cardiovascular Medicine.

The journal features ar;cles including research, reviews and case reports peer-­‐reviewed by accomplished cardiologists in their respec;ve fields. Young authors, not only progress in publishing their findings, but also engage in a peer review process which can only be beneficial for their future, by developing their wri;ng skills.

However, the journal also caters for junior readers by featuring a number of educa;on ar;cles on topics per;nent to the undergraduate curriculum. Moreover, a number of quizzes and other alterna;ve teaching methods are employed to appeal to different styles of learning. Last but not least, blog entries, elec;ve experiences and opinion ar;cles are incorporated to promote and enhance student interac;on.

On behalf of the editorial team, I hope you enjoy reading our journal and I assure you that we will do our best to live up to your expecta;ons.

Mahvesh Rana Javaid Chief Lead Execu4ve Editor Founder & President of Bri;sh Undergraduate Cardiovascular Associa;on (BUCA)

Rafail Angelos Kotronias Chief Editor BUCA Vice-­‐President

Marilena Giannoudi Chief Editor BUCA Research Officer

4

OUR HISTORY The BriKsh Undergraduate Cardiovascular AssociaKon (BUCA) has become the first student-­‐led plaVorm for medical students and junior doctors interested in cardiovascular medicine, including cardiology and cardiac/cardiothoracic surgery. It was founded in November 2012 by Mahvesh Rana Javaid, currently a final medical student at Barts & The London, and the Student RepresentaKve for the Cardiology Council at Royal Society of Medicine (RSM) for the last 3 years.

With no such associaKon or society of this type having previously existed, the BUCA founder felt it was essenKal to fill this gap. With great iniKaKve and support from cardiologists, the founder recruited a brand new commi\ee in March 2013 and with success an AGM was held to elecKng the next commi\ee in March 2014. Over the years, BUCA has been excelling in becoming successful and is working towards finalising its affiliaKon with the BriKsh Cardiovascular Society (BCS). On top all this, BUCA ensures there is cardiac society at every university, and so far BUCA leads 25 cardiac socieKes across the UK. This solid network allows the cardiac socieKes to be supported academically and financially when undertaking events at a local levels and then all to come together once a year at the BUCA RepresentaKves Day.

BUCA has many aims and acKviKes throughout each academic year as stated on our website. We have aims to provide talks and courses, along with organising the biggest event of the year that unites us all annually:

The joint InternaKonal and NaKonal Undergraduate Cardiovascular Conference. For consecuKve years, we have ran two InternaKonal and 3 NaKonal Conferences, with medical students and junior doctors a\ending from across the world including Europe, Africa and Asia. We have provided this opportunity for anyone who is interested or wants to find out about if cardiovascular medicine is for them, plus creaKng the path for those who want the chance to show their research. We are able to run such a high class conference with team work from the hard-­‐working commi\ee and volunteers from all our university cardiac socieKes across the UK. There are real cardiac simulators and interesKng workshops supported by the BriKsh Junior Cardiologists' AssociaKon (BJCA); an associaKon providing excellent support. In addiKon to these opportuniKes, we provide talks by leading cardiologists on the hot topics in the field adapted and delivered at the levels for medical students and junior doctors.

From the successful conference last year, it is an absolutely exciKng and inspiraKonal day for all those who a\end. BUCA will conKnue to prosper and expand in cardiovascular medicine for all medical students and junior doctors across the world. We look forward in seeing you all do well in cardiovascular medicine and we will always be there to support you, the next generaKon in cardiovascular medicine.

Mahvesh Rana Javaid Founder & President of Bri;sh Undergraduate Cardiovascular Associa;on (BUCA)

5

Health Economics In Cardiology Policy DecisionMaking: An Introductory Article based on Transcatheter Aortic Valve Implantation Rafail Kotronias1 1. Medical Student, Keele University, United Kingdom

Introduction In recent years, there has been a rise in the incidence of cardiovascular disease, consequently the esKmated healthcare expenditure is approaching an average of 10% of the Gross DomesKc Product (GDP) in OrganisaKon for CooperaKon and Economic Development (OECD) countries (UK, France, Germany, United States among others).1 While the supply and demand for healthcare services is increasing year afer year, the resources available to finance them are limited.

Indeed, one of the ways that healthcare systems can maintain quality, is to improve the economic efficiency of their investments through healthcare orientated economic evaluaKon. This short arKcle will introduce healthcare economic principles that guide policy decision-­‐making.

In health economics 3 types of data are needed in order to make a decision regarding new therapeuKc strategies: i) clinical data, ii) cost-­‐effecHveness data and iii) cost data.1-­‐2 This arKcle will use TAVI as a case study.

I) Clinical Data Clinical data are really important for assessing the efficiency, clinical effecKveness and safety of an intervenKon. These data should be collected from double blinded randomized controlled trials (RCTs) such as, in the case of the TAVI, the Placement of AoRTic TraNscathetER (PARTNER) trial, however, data are also derived from naKonal registries such as the French AorKc NaKonal CoreValve and Edwards (FRANCE) or the Edwards SAPIEN AorKc Bioprosthesis European Outcome (SOURCE).2-­‐5 The PARTNER trial authors, using 1-­‐year and later 2-­‐year mortality data as their single composite outcome, argued the following:

i.

TAVI (or TAVR) is more effecKve than standard treatment in paKents meeKng pre-­‐operaKve and other criteria for Surgical AorKc Valve Replacement (SAVR) ii. TAVI is not inferior to SAVR in the group of paKents qualifying for SAVR.2,6-­‐7

Reynolds et al. also showed improved outcomes regarding quality of life; another important decision-­‐making parameter.8 The above literature was pivotal in establishing the current group of paKents eligible for TAVI, although recent research and development are paving the way for an expansion of the inclusion criteria to possibly encompass moderate and low risk paKent groups.9

II) Cost-Effectiveness Analysis

A. Analysis with Primary PaKent Data This analysis aims to compare the clinical and economic data of different intervenKons using a measure known as Incremental Cost-­‐EffecKveness RaKo (ICER). This is the raKo of the cost difference over the benefit difference of the two compared intervenKons.1 The two acceptable measures of benefit in health economics and healthcare policy are life to year gained (LYG) and quality-­‐adjusted life to years (QALY). In other words, an ICER is a number which aids a government/policymaker to judge whether an intervenKon is worth its money.

The PARTNER trial authors, who compared TAVI with standard therapy in paKents not qualifying for SAVR, reported an ICER for TAVI of US$50,200 per LYG or US$61,889 per QALY.10

B. Analysis using Health Econometric Modeling This is an alternaKve way of measuring cost-­‐ effecKveness by inserKng and altering different parameters in a given model, whose purpose is to simulate data derived from paKents. Brunn et al

6

suggest that all studies agreed TAVI is a cost effecKve approach for surgical turndowns; on the contrary, when comparing TAVI to SAVR results are mixed, underlining the weaknesses of using econometric models.2 This very weakness lies with the way econometric models are made; the parameters might not be chosen appropriately or be weighed accurately and the pa\erns developed do not reflect anomalies that exist in a populaKon. Due to the nature of an econometric model – a mathemaKcal method of predicKng economic variables in the future – one small mistake at the outset will be propagated into the “future” creaKng a big discrepancy from reality. These discrepancies are also exacerbated by the inter-­‐group method variability as they choose different parameters or weigh them differently.

All the above introduce a variability that makes cost-­‐effecKveness more reliably calculated using primary paKent data than modelling. However, the la\er should not be discarded as a method of assessing cost-­‐effecKveness as many intervenKons cannot be assessed using primary paKent data due to the shear cost of running the research projects for the collecKon of such data.

II) Cost Data A range of prices from US$40,61913 to US$78,54210 have been calculated from different studies.

However, the heterogeneity of the data could be a\ributed to differences in healthcare costs and naKonal healthcare system structures among the countries where TAVI is available. Nonetheless, cost data are important for policy decision makers as well as hospital managers in order to devise their annual budgets.2

Conclusion All in all, due to the finite resources available and the opportunity costs involved with resource allocaKon, economic data are needed to embark into objecKve and standardised public health decision-­‐making. However, the existence of other, non-­‐economic factors is a glimpse of hope that “numbers” might be set aside when ethical and paKent-­‐centered arguments are made for new therapies that can improve the health outcomes of the populaKon.

References 1. Maniadakis N, Vardas P, Mantovani LG et al. Economic evaluaKon in cardiology. Europace, 2011; Suppl 2:ii3-­‐8.

2. Brunn M, Durand-­‐Zaleski I. Basic Principles of Health Economics Applied – How to Assess if Transcatheter AorKc Valve ImplantaKon is Worth the Investment. Interven;onal Cardiology Review, 2013; 8(8): 135–9.

3. Lefèvre T, Kappetein AP, Wolner E, et al. One year follow-­‐up of the mulK-­‐centre European PARTNER transcatheter heart valve study.

European Heart Journal, 2011;32(2):148–57.

4. Gilard M, Eltchaninoff H, Iung B, et al. Registry of transcatheter aorKc-­‐valve implantaKon in high-­‐risk paKents. New England Journal of Medicine, 2012;366(18):1705–15.

5. Thomas M, Schymik G, Walther T, et al. One-­‐year outcomes of cohort 1 in the Edwards SAPIEN AorKc Bioprosthesis European Outcome (SOURCE) registry: the European registry of transcatheter aorKc valve implantaKon using the Edwards SAPIEN valve. Circula;on, 2011;124(4): 425–33.

6. Leon MB, Smith CR, Mack M, et al. Transcatheter aorKc valve implantaKon aorKc stenosis in paKents who cannot undergo surgery.

New England Journal of Medicine, 2010;363(17):1597–607.

7. Kodali SK, Williams MR, Smith CR, et al. Two-­‐year outcomes afer transcatheter or surgical aorKc-­‐valve replacement. New England Journal of Medicine, 2012;366(18):1686–95.

8. Reynolds MR, Magnuson EA, Wang K, et al. Health-­‐related quality of life afer transcatheter or surgical aorKc valve replacement in high-­‐risk paKents with severe aorKc stenosis: results from the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial (Cohort A). Journal of the American College of Cardiology, 2012;60(6):548–58.

9. Neragi-­‐Miandoab S, Michler RE. A review of most relevant complicaKons of transcatheter aorKc valve implantaKon. ISRN Cardiology, 2013; doi: 10.1155/2013/956252.

10. Reynolds MR, Magnuson EA, Wang K, et al. Cost-­‐effecKveness of transcatheter aorKc valve replacement compared with standard care among inoperable paKents with severe aorKc stenosis: results from the placement of aorKc transcatheter valves (PARTNER) trial (Cohort B). Circula;on, 2012;125(9):1102–9 11. .Devlin N, Parkin D. Does NICE have a cost-­‐effecKveness threshold and what other factors influence its decisions? A discrete choice analysis. Discussion Paper Series, No. 03/01.

12. Dakin H, Devlin N, Feng Y et al. The influence of cost-­‐effecKveness and other factors on NICE decisions. HERC Research Paper 05/14.

Oxford: Health Economics Research Centre.

13. Chevreul K, Brunn M, Cadier B, et al. Cost of transcatheter aorKc valve implantaKon and factors associated with higher hospital stay cost in paKents of the FRANCE (FRench AorKc NaKonal CoreValve and Edwards) registry. Archives of Cardiovascular Diseases, 2013;106(4): 209–19.

7

Cardiopulmonary Bypass and Acute Kidney Injury Shruti Jayakumar1 1. Medical Student, King’s College London, University of London, United Kingdom

Abstract With a rise in the number of annual cardiothoracic surgeries, the cardiopulmonary bypass (CPB) machine has become ever so crucial to the successful compleKon of operaKons. However, it is not without risks, one of which is acute kidney injury (AKI). There are several risk factors associated with CPB induced AKI including; gender, age, type of surgery and most importantly, increased cardiopulmonary bypass duraKon. Whilst the actual cause and pathogenesis of post CPB AKI is largely unknown, there are various mechanisms thought to contribute to kidney damage. These include; a strong systemic inflammatory, haemodynamic instability, high microembolic load and nephrotoxins Introduction The CPB pump takes over the funcKons of the heart and lungs and supports circulaKon extra-­‐corporeally while the surgeon operates on the heart. The CBP machine comprises of a network of tubing made from poly vinyl chloride and various components that enable this. It drains out venous blood, removes carbon dioxide and debri, oxygenates it and pumps it back into the arterial circulaKon at the a p p r o p r i a t e p r e s s u r e . S i m u l t a n e o u s l y , a cardioplegic soluKon is administered to the coronary circulaKon, to stop the heart, allowing the surgeon to operate on a sKll field.

Risk Factors for CPB mediated AKI There are many risk factors for CPB induced AKI as summarized in Table 1. The factors with the highest correlaKon to the development of AKI were shown to be; 70 years of age and above as well as duraKon of CPB, which also increased the severity of AKI. Hypertension, atherosclerosis, or other peripheral artery disease is also linked to increased risk, as is preexisKng diabetes mellitus, reduced lef ventricular funcKon and congesKve heart failure.

This is because any issues with circulaKon and perfusion to the kidney will increase the suscepKbility of the kidney to injury1. The type of surgery has also shown to have an impact as they are associated with larger amounts of microemboli and debris, which may then cause an obstrucKon in the kidney and cause ischaemia. The transfusion of red blood cells may also increase the risk of AKI, due to accumulaKon of nephrotoxins.

Pathogenesis Although no single key mechanism behind post cardiac bypass AKI is currently known, the underlying pathogenesis is thought to be mulKfactorial.

T h e s e i n c l u d e i n fl a m m a t o r y r e s p o n s e s , haemodynamic instability, high micro embolic load and nephrotoxin-­‐mediated damage. These factors together cause harm to kidney from many angles, resulKng in tubular and glomerular injury.

Inflamma;on A strong inflammatory response is triggered in paKents undergoing cardiopulmonary bypass due to a combinaKon of several factors. First of all, there is the inflammaKon in response to the surgical trauma itself. However, this is fairly localized to the site of the operaKon and does not usually cause systemic inflammatory response syndrome (SIRS.) On the other hand, the contact of blood components with CPB tubing (polyvinyl chloride) incites a strong inflammatory response involving the complement system, neutrophils, endothelial cells and reacKve oxidaKve species, and inflammatory mediators and can lead to SIRS.1 CPB increases neutrophil count and acKvates them as well as increasing CD11b expression. As a result, there is increased neutrophil degranulaKon as well as protease enzyme release, causing tubular and glomerular injury2. Furthermore, CPB has been shown to induce the producKon of reacKve oxidaKve species (ROS) and decrease anK-­‐ oxidaKve capacity. This means there is increased oxidaKve stress, which causes endothelial injury and has been shown to cause tubular necrosis and 8

Risk Factors

Effect

Gender

Females are more at risk

Age

Risk increased with age afer 70 years

CPB DuraKon

Increased CPB duraKon increases AKI risk but also increases AKI severity

Serum CreaKnine

Pre-­‐operaKve level >1.2mg/dl increases risk

PreoperaKve Peripheral Artery Disease Eg. Hypertension/ atherosclerosis

Increases risk

Diabetes Mellitus

Increases risk, especially if uncontrolled

Chronic ObstrucKve Pulmonary Disease

Increases risk

Reduced Lef Ventricular FuncKon

Increases risk

Type of Surgery

Emergency surgery increases risk Valve surgery increases risk

PreoperaKve Atrial FibrillaKon

Increases risk

PreoperaKve Intra-­‐AorKc Balloon Pump

Increases risk

Red Blood Cell Transfusion

Increases risk

Table 1: Effects of Various Factors on Cardiopulmonary Bypass Induced Acute Kidney Injury

and has been shown to cause tubular necrosis and plays a major role in AKI development.3 Lastly, CPB also acKvates many inflammatory mediators and causes producKon of cytokines including Interleukin 6 (IL-­‐6,) Interleukin 18 (IL-­‐18,) and Tumour Necrosis Factor (TNF.) IL-­‐6 and TNF have been shown to decrease renal microcirculaKon and cause tubular injury. IL-­‐18 has been shown to mediate injury through acKvaKon of apoptosis in renal tubular epithelial cells.4

Haemodynamic Instability Normally the kidneys are autoregulated within a mean arterial pressure range of approximately 80mmHg to 180 mmHg. In other words, kidneys maintain a constant blood flow and GFR within this pressure range, which protects them against ischaemia. However, the perfusion pressure during CPB is ofen at the lower end of this range, and someKmes below it. Furthermore, a crystalloid sodium lactate soluKon is added into the CPB circuit to fill up the volume of the circuitry and prevent hypovolaemia. This causes diluKon of red blood cells and therefore a reduced haematocrit, resulKng in anaemia.

Therefore, even at perfusion pressures within autoregulatory range, the kidney is faced with ischaemia due to lowered haematocrit from haemodiluKon. This haemodynamic instability can cause renal ischaemia and therefore tubular necrosis and kidney injury.2

Microemboli Due to the nature of the operaKon, there may be increased amounts of micro emboli in the circulaKon. There may be gaseous bubbles or parKculate ma\er from surgical debris such as the tubing, or even bits of free Kssue resulKng from operaKve trauma. Moreover, during the cross clamping of the aorta or proximal grafing in CABG, cholesterol plaques may break loose in atheroscleroKc paKents and cholesterol micro emboli may form. The micro emboli can then block renal capillaries and cause glomerular damage.5

Nephrotoxins In addiKon to the hypoperfusion, ischaemia, micro emboli and inflammatory damage, the kidney is exposed to nephrotoxins, which further contributes to the kidney injury. AdministraKon of nephrotoxic drugs, such as certain anKbioKcs (eg. Gentamicin) and non-­‐steroidal anK-­‐ inflammatory agents (NSAIDs), can exacerbate kidney injury. However, on its own this will cause very li\le damage, if at all. Rather, during CPB the major nephrotoxins arise from endogenous molecules, resulKng in pigment nephropathy.2

9

Pigment nephropathy is renal tubular injury as a result of free haemoglobin or free myoglobin and is an important contributor to AKI. CPB can cause some haemolysis as the blood is passed through filters and pumps, causing mechanical destrucKon of the erythrocytes, resulKng in free haemoglobin.

Small amounts of free haemoglobin will become bound to haptoglobin, taken to the liver and metabolized, thereby never reaching the kidney.

However, in cases of increased haemolysis, the haptoglobin may become saturated. As a result, the excess haemoglobin will not become bound to it, and won’t be transported to the liver to be metabolized, remaining free to circulate.3

When there are large quanKKes of free haemoglobin, it will get filtered through the glomerulus. An acid environment, such as that found in urine, can then cause the formaKon of met-­‐haemoglobin, which precipitates in the tubules resulKng in cast formaKon, occlusion of the tubules and finally, filtraKon failure.

AddiKonally, ischaemia potenKates the formaKon of casts, which further increases tubular obstrucKon. Because CPB paKents usually also have some degree of renal ischaemia, haemoglobin pigment nephropathy is one of the central mechanisms of the pathogenesis of CPB induced AKI.6

Haemoglobin is capable of releasing iron from the haem molecules, which can then go on to form oxygen radicals. Iron in its ferric form (Fe3+) is known to catalyze the Haber-­‐Weiss reacKon, as shown below:

O2•-­‐ + H2O2 → OH-­‐ + •OH + O2 As seen, this reacKon yields hydroxyl radicals (•OH), which have destrucKve effects on the renal tubules. This reacKon is pH dependent, sKmulated at an acidic pH. Furthermore, through oxygen radicals, iron promotes lipid peroxidaKon, which is the oxidaKve degradaKon of lipids. This leads to cell membrane damage and therefore cellular injury. Lastly, free haemoglobin is potent in scavenging endothelium-­‐derived nitric oxide, w h i c h u l K m a t e l y l e a d s t o i n c r e a s e d vasoconstricKon and platelet acKvaKon. This causes decreased blood flow, leading to ischaemia.3

Red blood cells may also increase risk of pigment nephropathy because during storage they accumulate pro-­‐inflammatory molecules, free haemoglobin and free iron, lose their ability to generate nitric oxide, release procoagulant molecules, and deplete ATP and 2,3 BPG, making them nephrotoxic. 7

Conclusion The future holds more promise for the reducKon in CPB induced AKI, with the development of various techniques and equipment that remove factors contribuKng to pathogenesis. While current tubing consists of polyvinyl chloride, the future may see the development of tubing that is less immunoreacKve, which may reduce the strong inflammatory response seen in paKents undergoing CPB.8 Furthermore, there is an increased focus on leukocyte-­‐depleKng filters.

AcKvated leukocytes are known to contribute heavily to the inflammatory response induced by CPB, and contribute to renal injury. Therefore depleKng the leukocytes during the CPB process may reduce SIRS and have clinical benefits.9 Lastly, the development of minimally invasive procedures as opposed to a classical median sternotomy, may allow for surgery to be done without the use of a CPB pump altogether. For instance, transcatheter aorKc valve implantaKon (TAVI) is the replacement of the aorKc valve through a blood vessel as opposed to open-­‐heart surgery, which would require the CPB machine.

10

References

1. Abu-­‐Omar, Yasir, and Chandana Ratnatunga. "Cardiopulmonary Bypass and Renal Injury." Perfusion 21 (2006): 209-­‐11.

2. Rosner, Mitchell H., and Mark D Okusa. "Acute Kidney Injury Associated with Cardiac Surgery." Clinical Journal of the American Society of Nephrology 1.1 (2006): 19-­‐32.

3. Ronco, C., R. Bellomo, and John A. Kellum. Cardiopulmonary Bypass. Acute Kidney Injury. Basel: Karger, 2007. 342-­‐48.

4. Parikh, C. R., J. Mishra, and H. Thiessen-­‐Philbrook. "Urinary IL-­‐18 Is an Early PredicKve Biomarker of Acute Kidney Injury afer Cardiac Surgery." Kidney Interna;onal 70.1 (2006): 199-­‐203. Web. 5. HedayaK, N., JT Sherwood, SJ Schomisch, JL Carino, and AH Markowitz. "Axillary Artery CannulaKon for Cardiopulmonary Bypass Reduces Cerebral Microemboli." The Journal of Thoracic and Cardiovascular Surgery 128.3 (2004): 386-­‐90.

6. Haase, M., A. Haase-­‐Fielitz, and R. Bellomo. "Cardiopulmonary Bypass, Hemolysis, Free Iron, Acute Kidney Injury and the Impact of Bicarbonate." Cardiorenal Syndromes in Cri;cal Care 165 (2010): 28-­‐32.

7. KarkouK, K., D. N. Wijeysundera, T. M. Yau, J. L. Callum, et al.

"Acute Kidney Injury Afer Cardiac Surgery: Focus on Modifiable 10 Risk Factors." Circula;on 119.4 (2009): 495-­‐502.

8. Gourlay, TI, I. Samartzis, D. Stefanou, and K. Taylor. "Inflammatory Response of Rat and Human Neutrophils Exposed to Di-­‐(2-­‐ethyl-­‐hexyl)-­‐ phthalate-­‐plasKcized Polyvinyl Chloride." Ar;ficial Organs 27.3 (2003): 256-­‐60.

9. Bechtel, J.F.Ma\hias, Simone Mühlenbeina,Wolfgang Eichlerb et al.

"Leukocyte DepleKon during Cardiopulmonary Bypass in RouKne Adult Cardiac Surgery." Interac;ve Cardiovascular and Thoracic Surgery 12.2 (2010): 207-­‐12.

10. Thourani, VH, WB Keeling, and RA Guyton et al. "Outcomes of Off-­‐ pump AorKc Valve Bypass Surgery for the Relief of AorKc Stenosis in Adults. Annals of Thoracic Surgery 91.1 (2011): 131-­‐36.

Cardiac Screening in Athletes; High Profile with Big Barriers Rachel Wamboldt1 1. Medical Student, University of East Anglia, United Kingdom

Introduction When an athlete reaches an elite level in their career, they are viewed by society as indestrucKble or even immortal. The athleKc body is seen to be the pinnacle of health and wellbeing; therefore it is no surprise that when an athlete suffers from sudden cardiac death, it is met with an enormous amount of publicity and social anguish. Exercise is ofen used in medicine for primary and secondary prevenKon so when an athlete dies in compeKKon, it sends mixed messages to the public.

Sudden cardiac death (SCD) can be defined as an unanKcipated death, occurring with or without prodromal symptoms, in an individual with no previous history of cardiac disease.2 SCD is considered rare; however it is the leading cause of death in athletes during exercise.3 It can be triggered by several mechanisms including sympatheKc sKmulaKon, acute myocardial ischaemia due to coronary artery disease or due to abrupt changes in haemodynamic status which can result in ventricular arrhythmias.4,5

Causes of SCD in young athletes are due to abnormaliKes in cardiac structure, electrical conducKon or due to acquired causes, such as infecKon, toxins or trauma.3 The most common c a u s e o f e x e r c i s e -­‐ r e l a t e d S C D a r e cardiomyopathies such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC).3

InteresKngly, these condiKons are more common in athletes that parKcipate in start and stop sports, as opposed to endurance sports, as they are usually naturally selected out of these sports due to the limitaKons of their disease.3

The Big Debate The debate conKnues as to whether ECG screening should be mandatory for all elite athletes and whether pre-­‐parKcipaKon screening programs should be made available to young athletes. Italy has led the way in the promoKon of cardiac screening in athletes. One of the most important studies of SCD was completed by Corrado et al.

(2006) between 1979-­‐1999, in the Veneto region of Italy. This study showed that since the introducKon of a naKonwide cardiac screening program for young athletes, the overall incidence rate for sudden death from cardiomyopathies had decreased by 89%, due to early detecKon and treatment.6 This degree of success however, has not been seen in other regions of the country.5

P r e -­‐ p a r K c i p a K o n s c r e e n i n g i s c u r r e n t l y recommended by various organisaKons and sports governing bodies, including the European Society of Cardiology and the InternaKonal Olympic Commi\ee; however the definiKon of the screening program and the enforcement of such a program varies widely amongst naKons.3 Italy has led the way with cardiac screening programs in athletes. Their current protocol involves an extensive history, physical examinaKon and

extensive history, physical examinaKon and 12-­‐lead

ECG for all compeKKve athletes.3 This is in comparison to the United States, who have a 12-­‐point screening protocol that encompasses a history and examinaKon

without the addiKon of the 12-­‐lead ECG.3

The Road Blocks Although there has been plenty of evidence illustraKng the benefit of cardiac screening programmes in athletes, it is not completely cut and dry. The major barrier that advocates have faced is that ECG screening programmes do not meet the WHO Screening Criteria, specifically that the health problem needs to have a moderate prevalence.9

It was also shown in early economic analyses that screening would not meet cost benefit targets; however, they have mostly focused specifically on HCM rather than the mulKtude of cardiac condiKons that can be picked up on a 12-­‐lead ECG.9 A more recent economic analysis in the US esKmated the direct cost of a cardiac screening program in high school athletes would be $US44,000 per life year saved (the US usually spends $US 20 000 to $US 100,000 on intervenKons that add one year of disease free life).9, 10 As SCD commonly occurs in young athletes, in their early 20s, prevenKng such an event could extend their life by 60-­‐70 years.9 It can therefore be argued that any cost incurred by a screening program would surely be returned in producKvity.

Making a Difference Now Athlete deaths are rare, but because they occur at such a young age, they are ofen high profile cases in the media. Before the UK gets on board with cardiac screening, there needs to be clearer ECG criteria, be\er referral guidelines and more established care plans. For the Kme being it is important that all efforts are made to advocate for the placement of automated external defibrillators (AEDs) in as many public places as possible, especially in locaKons of athleKc compeKKon. Early CPR and defibrillaKon are essenKal to improving outcomes in young athletes with SCD. One study showed that when AEDs were used in US high schools, 23 out of 36 cardiac arrests (64%) survived to hospital discharge.3

The Kme of pre-­‐parKcipaKon cardiac screening is drawing close. Ongoing research into ECG interpretaKon is conKnually improving the sensiKvity of the tool.5 The debate conKnues; however there is a light at the end of the tunnel.

We just need to cross a few speed bumps to get there.

References 1) NHS Choices. Cardiovascular disease. h\p://www.nhs.uk/ CondiKons/cardiovascular-­‐disease/Pages/IntroducKon.aspx (accessed 19/09/2013 ).

2 ) S o v a r i A A . S u d d e n C a r d i a c D e a t h . h \ p : / / emedicine.medscape.com/arKcle/151907-­‐overview ; ;Last accessed 15/09/2014.

3) Chandra N, BasKaenen R, Papadakis M, Sharma S. Sudden Cardiac Death in Young Athletes; PracKcal Challenges and DiagnosKc Dilemmas. Journal of the American College of Cardiology 2013;61(10): 1027-­‐1040.

4) Asif I M, Drezner J A. DetecKng occult cardiac disease in athletes: history that makes a difference. Bri;sh Journal of Sports Medicine 2013;47(11): 669.

5) Perez M, Fonda H, Le V, MiKku T, Ray J, Freeman J V, Ashley E, Phil D, Froelicher V F. Adding an ECG to Pre-­‐parKcipaKon Exam in CompeKKve Athletes. Current Problems in Cardiology 2009;34: 586-­‐662.

6) Corrado D, Basso C, Pavei A, Michieli P, Schiavon M & Thiene G. Trends in sudden cardiovascular death in young compeKKve athletes afer implementaKon of a preparKcipaKon screening program. JAMA 2006;296(13): 1593-­‐1601.

7) Corrado D, Pelliccia A, Heidbuchel H, Sharma S, Link M, et al.

RecommendaKons for interpretaKon of 12-­‐lead electrocardiogram in the athlete. European Heart Journal 2010;31: 243-­‐259.

8) Pelliccia A, Di Paolo FM, Corrado D. Evidence for the efficacy of the Italian naKonal pre-­‐parKcipaKon screening programme for idenKficaKon of hypertrophic cardiomyopathy in compeKKve athletes. European Heart Journal 2006:27: 2196-­‐2200.

9) Shephard R A. Mandatory ECG Screening of Athletes. Is this QuesKon Now Resolved? Sports Medicine 2011;41(12): 989-­‐1002.

10) Fuller C. Cost effecKveness analysis of screening of high school athletes for risk of sudden cardiac death. Medical and Science in Sports Exercise 2000;32: 887-­‐890.

11) Cardiac Risk in the Young. General Informa;on on Cardiac S c r e e n i n g . h \ p : / / w w w . c -­‐ r -­‐ y . o r g . u k / general_informaKon_on_cardiac_s.htm (accessed 17/09/2013) 12) Ve\er V L, Dugan N, Guo R, Mercer-­‐Rosa L, Gleason M, Cohen M, Vogel R L, Lyer R. A pilot study of the feasibility of heart screening for sudden cardiac arrest in healthy children. American Heart Journal 2011; 161 (5):1000-­‐1006.

12

An Elective Report in Cardiology Abishek Da\ani1 1. Foundation Year 1 Doctor, Princess Alexander Hospital (Harlow), United Kingdom

As a final year medical student, we had this inspiring opportunity to explore medicine in another country as part of an elecKve. I decided that I wanted to pursue my interest in cardiology but I wanted to do it in a way that would help me learn about a different healthcare system. My desKnaKon, I decided, was to be India at the Narayana InsKtute of Cardiac Sciences in Bangalore.

In India, cardiovascular disease certainly plays a major burden on health of the populaKon. Approximately 25% of deaths are thought to be due to cardiovascular disease and it is esKmated that within the next 10 years it will be the cause of mortality in 50% of people in India. With a populaKon of 1.2 billion, it is thought, astoundingly, that 60% of cardiovascular disease paKents reside in India.(1)(2)

When comparing the two countries, the UK has a cardiovascular disease age standardised mortality rate of 180 per 100,000, whereas India has a much greater rate of 405 per 100,000. In 2000, coronary heart disease caused 1.18 million deaths and stroke caused 0.45 million deaths.

Not only is cardiovascular disease more common in India, but it also seems to be occurring in a younger populaKon. Astonishingly, in India, 50% of deaths due to coronary heart disease occur in paKents under 70 years, whereas in the western world, only 22% of the deaths are in paKents under 70 years of age.(2)

Dr Devi She\y, chairman of Narayana Health, started the hospital in 2001 in Bangalore, India.

Narayana InsKtute of Cardiac Sciences is a specialist cardiac hospital that carries out 40 cardiac surgeries per day including both adult and paediatric, as well as doing several cardiac catherisaKons and stenKng procedures daily.

In India, tradiKonally the government hospitals usually provide care for those who cannot afford private care but the standard of care at these hospitals is not very high. This hospital, however, is a private hospital and sKll manages to provide care to people with low or no income at a very cheap cost. Indeed, some paKents are treated without charge if they are not able to pay. How is this achieved?

Dr She\y has decided to use economies of scale to keep costs low. By building very large hospitals that carry out the same procedures many Kmes per day, they are able to get discounts on the equipment required and thus reduce the cost of the treatment. For example, a normal hospital ICU in India will do 30 blood gas analyses per day, which for the paKent costs approximately Rs. 350-­‐400 (£3.50-­‐£4.00) each. However, at Narayana Health, there are more than 2000 blood gas analyses done each day. The hospital was able to negoKate with the manufacturer of the machine to provide the machines for free and then charge for the individual reagents instead.

This would now allow the hospital to charge the paKent only Rs 8.50 (£0.08) for each test, making the overall cost of the admission lower.(3)

13

My experience of cardiology in India is something that I will never forget. I think choosing a place for an elecKve isn’t easy as there are many different types of elecKves. I found that my elecKve allowed me to gain a be\er understanding of clinical cardiology but it also gave me an insight into healthcare in India that I would otherwise not have achieved if I did my elecKve in this country. I would therefore recommend medical students to consider what they would like to achieve from the elecKve before making a decision on where to go.

Having researched the hospital before I arrived, I was sKll shocked at what I saw on Day 1. I arrived to a building located on the outskirts of Bangalore and was shown the way to the cardiology clinics where I faced hundreds of paKents waiKng to be seen by several cardiologists. I saw the professor of cardiology who explained my role and who then sent me to the CCU to learn about acute cardiology.

I spent most of my elecKve Kme examining paKents with interesKng clinical findings that I had only read about in textbooks. This included numerous paKents with the murmurs of mitral stenosis and pulmonary stenosis, added heart sounds and also signs of infecKve endocardiKs. One of the most interesKng paKents I saw was a paKent with Marfan syndrome who had developed a dilated cardiomyopathy. I also encountered an intriguing paKent with a pulmonary embolism as a complicaKon of Klippel-­‐Trenauny syndrome, a condiKon that involves venous malformaKons.

I was fortunate enough to get exposure to a vast amount of angiography which allowed me to get more familiar with analysis of angiograms and diagnosing coronary artery disease. I was able to spend Kme observing fascinaKng surgical procedures such as coronary artery bypass grafing and valve replacements.

Images of Narayana Ins;tute of Cardiac Sciences taken by Dr Abhishek Dacani References

1. WHO, World Health OrganizaKon, The Global Burden of Disease. h\p://www.who.int/topics/global_burden_of_disease/en/ (accessed 07/05/2014).

2. Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S. Epidemiology and causaKon of coronary heart disease and stroke in India. Heart 2008; 94:16-­‐26.

3. Mahajan-­‐Bansal N (2009). Dr Devi She\y’s mission of cheap healthcareh\p://ibnlive.in.com/news/dr-­‐devi-­‐she\ys-­‐mission-­‐of-­‐ cheap-­‐healthcare/96567-­‐7.html (accessed 03/05/2014).

14

An Elective Report in Cardiac Surgery Marilena Giannoudi1 1. Medical Student, Newcastle University, UK

From the Kme you start looking into medical schools, your elecKve is always at the back of your mind. This conKnues through all your exams and assignments, because you know that it will all be worth it in the end and you will have the opportunity to do what you really want to for a month or two. There are many factors that can influence your decision on the type of elecKve you want to undertake. For me, I wanted to go abroad and I wanted to the learn skills which I would need throughout my career. Where did I go? Canada!

This summer I was fortunate enough to spend four weeks with the cardiac surgery department at the Vancouver General Hospital. Having emailed my supervisor a few weeks before to introduce myself and to ask if I needed to bring anything, his response of ‘just comfortable shoes’ should have given it all away, and yet I was in for a surprise from my very first day.

Four weeks went by and I assisted in 31 surgeries in total. I went through three different pairs of shoes, saw roboKc surgery, and most importantly; I learnt! What I loved about the Canadian system is how hands on I was as a student. Not a single day went by where I didn’t scrub for surgery, which was not only so that I could see the surgery from nearer, but so that I could get involved. I sutured, helped in the se•ng up of the bypass procedure, found veins for bypass grafs, used the saw to open the thorax. At all Kmes, my seniors would describe and explain what was expected of me and what I had to do to get there. In this way I didn’t have the Kme to get nervous, I just had to get on with it!

My days were long and at Kmes Kring, however the learning experience was be\er than I ever could have hoped for. I lef my placement feeling confident, both in myself and the skills I acquired.

Yes, I had been to surgical conferences before and learnt how to Ke knots and suture, but it is only when this becomes a part of your every day rouKne that you truly feel that you have learned something.

A typical day on my elecKve was as follows: arrive in the hospital for 8am and head straight to the pre-­‐op assessment unit. Take a quick history from the first paKent on the list and follow them to surgery. Assist/ watch the staff prepare the paKent, whether this was watching the cardiac anaestheKst and discussing anaestheKc opKons or inserKng catheters and placing the paKent in the correct posiKon. I scrub in and assist in the surgery. I then follow the paKent through to cardiac intensive care for the hand over, before heading back to do the same again for the next case. Once a week we had grand rounds in the morning, where the surgeons, cardiologists and anaestheKsts could discuss parKcularly tricky cases, and the residents presented cases they had faced in the last week.

15

The Vancouver team is a parKcularly well-­‐ established unit with an excellent reputaKon. During my Kme there, I was able to see advances in surgery that to date I had only read about, including both roboKc and minimally invasive valve replacement surgery. For this I feel parKcularly lucky. However, I do not just have the academia to take away with me. The staff, both doctors and nurses, would go out of their way to welcome me and make sure that I was learning. I truly felt part of a team.

My weekends were always free to explore their beauKful country, full of things to see and do.

There is the sea, wildlife, and big city living; I was never bored.

If you are willing to learn, and to work long days, I would definitely recommend Canada as the elecKve desKnaKon for you. I may not have been snorkelling or on safari, but it is a beauKful country full of sites and wonderful opportuniKes both within and outside the workplace.

16

Topic: Diabetes Mellitus and Coronary Heart DiseaseMaking the Link Rachel Wamboldt1 1. Medical Student, University of East Anglia, UK

Introduction

Diabetes mellitus is a chronic condiKon resulKng f r o m t h e i n t e r p l a y b e t w e e n g e n e K c predisposiKon and environmental factors.

Diabetes occurs when there is a failure of the pancreas to secrete enough insulin to meet the needs of the body, alone or in combinaKon with insulin resistance. In 2011, the World Health OrganizaKon esKmated that there were approximately 366 million people living with diabetes worldwide.1 This is expected to rise to 552 million by the year 2030.1

The link between cardiovascular disease and diabetes mellitus has long been established.

Mortality as the result of heart disease and stroke are two to four Kmes higher in diabeKcs than non-­‐diabeKcs.2 Aside from having the disease, diabeKcs ofen possess aggregates of other cardiovascular risk factors including obesity, hypertension, dyslipidaemia and physical inacKvity.

The AssociaHon between Diabetes and CVD The pathogenic link between cardiovascular disease and diabetes is complex and involves an interacKon between oxidaKve stresses, endothelial dysfuncKon, risk factors (geneKcs and environmental) and a steady-­‐ state of low-­‐grade inflammaKon.2,3 Visceral fat deposiKon associated with obesity causes the maintenance of low-­‐grade i n fl a m m a K o n c a u s i n g i m m u n e c e l l recruitment and endothelial dysfuncKon. This leads to an increase in adhesion molecule expression and deficits in the secreKon of nitric oxide and prostacyclin, consequently promoKng atherogenesis in the coronary vessels and increasing the risk of myocardial infarcKon. 3 The heart is very responsive to insulin levels and as such hyperinsulinaemia caused by insulin resistance can induce hypertrophy of the cardiac myocytes.

Figure 1: A diagram summarising the possible risk factors for cardiovascular disease

17

Cardiovascular Autonomic Neuropathy

Cardiovascular autonomic neuropathy plays an enormous role in the survival of paKents with diabetes.

In the heart, the autonomic nervous system is responsible for controlling the heart rate (through the sinus node), ventricular filling volumes and systemic vascular resistance; therefore dysfuncKon of this system leads to increased arterial sKffness, lef ventricular hypertrophy and diastolic dysfuncKon in the ventricles.

2 Clinically, the paKents present with resKng tachycardia, postural hypotension, coronary vasomotor dysregulaKon (increasing the risk of silent myocardial infarcKons) and an increased risk of renal disease, stroke and sudden death. PaKents with this condiKon have a 5-­‐year mortality rate ranging from 16-­‐53%.2

TreaHng Diabetes Aggressively Several clinical trials, including the UKPDS and DCCT/ EDIC have illustrated the benefit of early intensive glycaemic control for type 2 diabeKcs in reducing the long-­‐term risk of cardiovascular events.5 The same risk reducKon was not achieved when intensive treatment was started in long-­‐term diabeKcs.6,7,8 It is postulated that this is the effect of ‘metabolic memory’; the effects of early exposure to a hyperglycaemic environment is remembered later by the blood vessels and organs.2

High blood pressure must also be aggressively treated in diabeKcs with both lifestyle modificaKon and drug therapy. NICE currently recommend a target blood pressure of <130/80 for all diabeKcs. Non-­‐ pharmacological management of blood pressure such as weight reducKon, smoking cessaKon, regular exercise and reduced alcohol consumpKon should also be encouraged. 2,3

Dyslipidaemia also adds to the overall cardiovascular risk with low levels of high density lipoprotein being an individual risk factor. One of the first staKn trials in type 2 diabeKcs (CARDS) showed a 37% reducKon in cardiovascular events and 48% reducKon in stroke when 10mg of atorvastaKn was used instead of a placebo.2

PerspecHve The incidences of both type 1 and type 2 diabetes conKnue to sore worldwide. PaKents with diabetes are at an increased risk of cardiovascular disease, especially in the presence of poor glycaemic control, hypertension, dyslipidaemia and obesity. There is currently a growing source of informaKon from clinical trials outlining the importance of early idenKficaKon and aggressive treatment of diabetes and its associated cardiovascular risk factors.

References: 1) InternaKonal Diabetes FederaKon. One Adult in 10 will have diabetes by 2030. [internet]. Available from: h\p://www.idf.org/media-­‐events/press-­‐ releases/2011/diabetes-­‐atlas-­‐5th-­‐ediKon 2) Matheus A S, Tannus L R M, Cobas R A, Palma C C S, Negrato C A, Gomes M B. Impact of Diabetes on Cardiovascular Disease: An Update. InternaKonal Journal of Hypertension. 2013.

3) Shiojima I, Walsh K. RegulaKon of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes and Development. 20:3347-­‐3365; 2006.

4) MarKn-­‐Timon I, Sevillano-­‐Collantes C, Segura-­‐ Galindo A, del Canizo-­‐Gomez F J. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World Journal of Diabetes. 5(4): 444-­‐470. 2014.

5) Holman R R, Paul S K, Bethel M A, Ma\hews D R, Neil H A W. 10-­‐Year follow-­‐up of intensive glucose control in type 2 diabetes, The New England Journal of Medicine. 359,(15): 1577–1589. 2008.

6) Duckworth W, Abraira C, Moritz T et al., Glucose control and vascular complicaKons in veterans with type 2 diabetes. The New England Journal of Medicine. 360 (2): 129–139. 2009.

7) Patel A, MacMahon S, Chalmers J, et al., “Intensive blood glucose control and vascular outcomes in paKents with type 2 diabetes,”The New England Journal ofMedicine, 358 (24): 2560–2572. 2008.

8) The AcKon to Control Cardiovascular Risk in Diabetes Study Group. Effects of Intensive Glucose Lowering in Type 2 Diabetes. The New England Journal of Medicine. 358: 2545–2559. 2008.

18

Topic: The Undergraduate Guide to Interpreting Angiograms Marilena Giannoudi1 1. Medical Student, Newcastle University, United Kingdom

As medical students, rarely will we have the opportunity to be taught how to read angiograms.

Coronary angiography is a technique which uses x-­‐ ray imaging to see the heart’s blood vessels. It can be performed for a number of reasons, including for symptoms of coronary artery disease, unstable angina as well as valvular problems which require surgery, among others.

The most important thing to remember as a student is that it will provide you with an image of the arteries of the heart, which will help us see if coronary arteries are blocked and how much blood is flowing through them.

The only way to become confident at interpreKng these angiograms is by pracKcing! Find an intervenKonal cardiologist or a cardiac surgeon and ask to spend Kme with them.

But unKl you do this here are some Kps for you to help in recognizing which artery is which.

1) How to recognize the leX vasculature from the right: Let us quickly re-­‐visit some basic anatomy.

The RIGHT coronary artery (RCA) will originate at the conus artery, above the right cusp of the aorKc valve. The branches of the RCA are the posterior descending artery and the right marginal artery.

The LEFT coronary artery arises from the aorta above the lef cusp of the aorKc valve. It bifurcates into the lef anterior descending (LAD) and the lef circumflex artery.

POINT TO REMEMBER: The lef hand side will have more branches than the right.

Image 1. Right coronary artery1. (see below, image 2, to compare with the led coronary artery and circula;on).

2) How to recognize the left anterior descending artery (LAD) from the left circumflex artery: The LAD will reach the bo\om of the heart at the lef ventricle.

In addiKon to this the LAD has two types of branches, the septals and the diagonals. The septal branches come off the LAD at a 90° angle, (to perforate and supply the anterior 2/3rds of the interventricular septum). On the other hand, the diagonals run along the surface of the heart (these branches will supply the lateral wall of the lef ventricle and the anterolateral papillary muscle).

19

Image 2. Led coronary artery and circula;on2

3) How to spot stenoses: The blood flow will not conKnue throughout the phase of the image of the angiogram, if you have total occlusion of an artery.

If there is less than 100% occlusion of an artery, a kink is usually evident in the artery wall. Remember that arteries can have both focal and diffuse narrowing.

N.B You will see collateral circula;ons forming, in areas where there has been a chronic obstruc;on of one of the coronary vessels.

4) How to spot a calcified artery:

Depending on how severe the calcificaKon is there are different things to see:

• Mild – densiKes noted only afer contrast injecKon • Moderate – densiKes noted only with cardiac moKon prior to contrast injecKon • Severe – Radio-­‐opaciKes noted without cardiac moKon prior to contract injecKon.

Image 3. Stenosis in the led circumflex artery 3

With these basic principles, go ahead and start pracKcing your own angiography interpretaKon!

References

Image 1: Percutaneous coronary intervenKon, h\p://en.wikipedia.org/wiki/Percutaneous_coronary_intervenKon#mediaviewer/File:HWI_PTCA.jpg. (Accsessed 18/09/2014)

Image 2: Coronary CatheterisaKon,.h\p://en.wikipedia.org/wiki/Coronary_catheterizaKon. (Accesssed 18/09/2014)

Image 3: Angiography coronary stenosis, h\p://commons.wikimedia.org/wiki/File:Angiography_coronary_stenosis_01.jpg.

(Accessed 18/09/2014).

20

Angiogram Case Image Quiz Marilena Giannoudi1 1. Medical Student, Newcastle University, UK

Case Scenario A 75 year old male presents to A&E with an acute onset chest pain which radiates down his lef arm. He is sweaKng and feeling nauseous. He has a history of hypertension, hypercholestrolaemia and angina. He is rushed to the cathether lab. Below is his angiogram.

(Image kindly provided by Dr James Wilkinson, Consultant Interven;onal Cardiologist, University Hospital Southampton and Wessex Cardiology. website: www.cardiology.co.uk)

Using the above angiogram, please answer the following quesKons (see overleaf for answers): 1. Which vessel is which?

2. Name two place of stenoses?

3. Is there calcificaKon?

21

Revealing the Angiogram: Answers Lef Lef Circumflex Circumflex Artery Artery

Lef Anterior Descending Right Circumflex Artery

There is a criKcal stenosis along one of the branches of the Lef Anterior Descending (LAD) artery (*). There is also an obvious in the lef coronary artery (*)

There appears to be no calcificaKon of the artery.

22

SUPPLEMENTS The following abstracts were accepted for the BriKsh Undergraduate Cardiovascular Conference 2013.

Figures and tables for abstracts will be available online www.bucardiology.org.uk.

ORAL PRESENTATIONS O1 – EUROSCORE II SCORES AMONG PATIENTS GOING FOR LEFT MAIN STEM PCI IN MALAYSIA. A NCVD-­‐PCI ANALYSIS Chin KP, Ang BH, Chan CC, Tan DWJ, Chee KH

IntroducHon: Coronary artery bypass grafing (CABG) is tradiKonally regarded as the standard of care for paKents

with lef main stem (LMS) stenosis. With the introducKon of drug eluKng stents, there is now an increasing trend to perform percutaneous coronary intervenKon (PCI) for LMS stenosis.

ObjecHve: The aim of this retrospecKve cohort study is to idenKfy the prognosKc factors that are able to predict both early and mid-­‐term mortality in paKents who have underwent PCI for LMS disease.

Methods and Results: The studied populaKon comprised of 291 paKents who underwent PCI on LMS in Malaysian NCVD-­‐PCI registry between years 2007 to 2010.

Results: The observed post procedure, 30 days, 6 months, 1 year and 3 years mortality rate was 4.5%, 4.8%, 4.8%, 4.8% and 5.4% respecKvely. In-­‐stent re-­‐stenosis at 3 years was 4.4%. Recent myocardial infarcKon (OR 3.5), ejecKon fracKon of 40% and below (OR 18.1), acute coronary syndrome (OR 4.9) and cardiogenic shock (OR 23.1) on admission are the potenKal predictors of post procedure death. MulKvariate analysis showed that ejecKon fracKon of 40% and below as the significant (p-­‐value <0.0001) independent clinical predictors of post procedure (adjusted OR 15.3). Using receiver-­‐operator characterisKcs (ROC) curves, EuroSCORE II demonstrated a high predicKve value for both post procedure and 1 year mortality (AUC>0.8, p-­‐value <0.0001).

Conclusion: EuroSCORE II has high predicKve value in 30 days and 1 year mortality post PCI in paKents with LMS disease.

23

O2 -­‐ ACUTE ISCHAEMIC STROKE AND MICRORNA: A NOVEL BIOMARKER? Groome C, Dawson J, Work L, Breen C

Background: MicroRNA expression is altered afer stroke, although whether this differs across stroke subtypes, with severity of stroke or has potenKal to provide prognosKc and diagnosKc informaKon is unclear. We therefore invesKgated microRNA profiles in paKents with suspected stroke, including a comparison across stroke sub-­‐types.

Methods: PaKents with suspected stroke were recruited from the Western Infirmary in Glasgow, and assigned to either a definite stroke (n=55), possible stroke (n=24), or non-­‐stroke group (n=17). The stroke group was further subdivided according to the TOAST criteria: cardioembolic (n=15), large artery (n=13), small vessel (n=16), and unclassified (n=11). Blood samples were taken post-­‐stroke at numerous Kme points and day 7 samples were only analysed in this study. MicroRNA was extracted from serum samples and the concentraKon determined using nanodrop spectrophotometry, with subsequent reverse transcripKon and real-­‐Kme quanKtaKve polymerase chain reacKon for specific microRNA probes. microRNA levels were standardised to an exogenous loading control or "housekeeper" gene, viz. c-­‐elegans microRNA-­‐39.

Results: There was no staKsKcally significant difference between the expression levels of microRNA between definite strokes, possible strokes, and non-­‐stroke paKents. However micoRNA-­‐139-­‐5p displayed a 1.8 fold difference between large artery strokes and the non-­‐stroke controls (p=0.003). No further observaKons and comparisons between stroke groups and the control populaKon demonstrated any significant fold-­‐changes.

Conclusion: Our results suggest that microRNA profiles differ across stroke subtypes and that this must be accounted for in design of future studies. microRNA-­‐139-­‐5p was significantly increased in large artery strokes. MiR-­‐139-­‐5p is involved in the regulaKon of many genes within the body, including: THBS1 (mediates cell-­‐to-­‐cell interacKons), MYC (role in cell cycle progression, apoptosis, and cellular transformaKon) PTGS2 (inflammaKon and mitogenesis), and CDKN1B (cell cycle progression). This creates a picture that this miRNA has regulatory powers in cell turnover and repair that may prove useful in responding to damage resulKng from acute ischaemia. Futhermore, it has been linked to the regulaKon of neuronal apoptosis. This may offer support for Kghtening miRNAs relaKonship with stroke pathogenesis and its appropriateness in serving as a biomarker.

24

O3 -­‐ BLEEDING COMPLICATION IN AORTIC SURGERY WITH OR WITHOUT APROTININ

CurKs A, Rajakaruna C

Background: AproKnin (Trasylol) is widely acknowledged to reduce bleeding and transfusion requirements in coronary artery bypass graf surgery however the evidence is limited and conflicKng in aorKc surgery.

There is now also evidence that aproKnin may be associated with increased renal failure, stroke and mortality rates. This study aims to determine whether aproKnin causes a reducKon in bleeding complicaKons in adult paKents undergoing aorKc surgery.

Methods: This is a single centre retrospecKve cohort study including 281 consecuKve adults undergoing aorKc surgery from August 2004 to December 2010 at the Bristol Heart InsKtute. Of these, 105 (37.4%) received aproKnin and 176 (62.6%) did not. Data was collected using surgical, biochemical and pathological databases, and intensive care observaKonal charts. The primary outcome was bleeding complicaKon consisKng of (i) post-­‐operaKve blood loss; (ii) transfusion requirements and (iii) haemoglobin reducKon. Further complicaKons were also considered. StaKsKcal analysis was completed using the Mann Whitney U test for conKnuous data and the Chi-­‐squared test for categorical data.

Results: Baseline characterisKcs and perioperaKve variables were similar between the two groups allowing further analysis to be undertaken. The total blood loss was only marginally lower in the aproKnin group (750 vs. 762.5mL) which did not cause a significant (P >0.05) difference in the percentage haemoglobin reducKon following surgery (28.6% vs. 29.7%) (Table 1). There was a non-­‐significant reducKon in blood product transfusions in the aproKnin group (52.4 vs. 59.1%) including fewer RBC transfusions (42.9 vs.

52.8%) and platelet transfusions (17.1 vs. 17.6%). However, more aproKnin group paKents received fresh frozen plasma (27.6 vs. 19.9%) and cryoprecipitate (6.7 vs. 4.5%) but this was not significant (Figure 1).

More control group paKents had to return to theatre for bleeding or tamponade (7.0 vs. 4.8%) but this was also not significant. Renal failure, stroke and hospital mortality rates were all similar between the two groups.

Conclusion: This is now the largest study to explore the use of aproKnin in aorKc surgery. Our results do not support the use of aproKnin in aorKc surgery as bleeding complicaKons were not significantly reduced in the aproKnin group. However, we find no evidence that aproKnin is associated with renal failure, stroke and death, as has been previously described in the literature.

25

26

O4 -­‐ HAEMODYNAMIC MECHANISMS UNDERLYING ESSENTIAL HYPERTENSION CHANGE ACROSS THE ADULT AGE-­‐SPAN: THE ANGLO-­‐CARDIFF COLLABORATIVE

Coumbe B, McEniery C, Maki-­‐Petaja K, Wilkinson I.

IntroducHon: EssenKal hypertension is a common condiKon and a major modifiable risk factor for cardiovascular disease. Although ofen viewed as a uniform condiKon, essenKal hypertension encompasses a number of disKnct pa\erns of blood pressure (BP) elevaKon, the prevalence of which appears to vary with age. We hypothesized that different haemodynamic mechanisms account for age-­‐related differences in BP phenotypes and our aim was to test this hypothesis in a large sample of individuals covering the adult age-­‐span.

Methods: Detailed haemodynamic data including seated (clinic) BP, cardiac output (CO) and stroke volume (SV), peripheral vascular resistance (PVR) and aorKc pulse wave velocity (aPWV), a robust measure of aorKc sKffness, were available in 5337 individuals (2381 males), aged between 18-­‐92 years. All individuals were free of cardiovascular disease and medicaKon. Data was straKfied according to age, gender and BP phenotype, on the basis of clinic BP, as follows: normotensive (NT), isolated systolic hypertension (ISH), systolic diastolic hypertension (SDH) and isolated diastolic hypertension (IDH). Significance was determined using one-­‐way ANOVA (P<0.05).

Results: The analysis confirmed previous findings regarding the distribuKon of hypertensive phenotypes across the adult life span with ISH being predominant in younger and older individuals and SDH being predominant in middle aged individuals. Within the younger populaKon there was a preponderance of males over females in ISH paKents (11:1), a\ributed to elevated CO and SV, confirming our previous findings (Fig.1 and Fig.2). In females SDH and IDH were more common and associated with elevated PVR and aorKc sKffness. However, within the female ISH populaKon there was an unusual phenotype with elevated cardiac output afer correcKon for BMI and heart rate (NT: 6.58±1.50 ISH: 9.32±3.13, P<0.001) (Fig. 2). In individuals over 60 the most common hypertensive phenotypes in males and females was ISH. In contrast to their younger counterparts there was no bias towards men present in older ISH paKents (1:1).

Older ISH paKents were characterised by markedly elevated aPWV compared with NTs (F: NT:8.24±1.88, ISH: 9.78±2.22, P<0.001 and M: NT:8.68±2.06, ISH: 10.08±2.47, P=0.007).

Conclusion: The prevalence of different BP phenotypes varied across the adult age span in males and females were associated with disKnct haemodynamic pa\erns. This data suggests that physiological profiling and targeKng therapy towards the underlying haemodynamic abnormality may be a worthwhile strategy with which to be\er idenKfy and intervene on this important risk factor.

27

28

O5 -­‐ SOCIAL DEPRIVATION AND ACCESS TO CARDIAC RESYNCHRONISATION THERAPY Cambell N, Pates K.

Background: Cardiac resynchronisaKon therapy (CRT) has been shown to significantly improve all-­‐cause mortality and morbidity in selected paKents with heart failure when compared with opKmal pharmacological therapy alone (NICE 2014). There is a wide variaKon in CRT implant rates across different geographical areas in England. We invesKgated whether social deprivaKon affects access to CRT in the English NaKonal Health Service.

Methods: CRT implant rates were collected for 152 primary care organisaKons (PCOs). The relaKve geographical need for CRT was determined using emergency heart failure admission rates (Public Health England, 2011) and the implant rate was adjusted accordingly. The Rank Average Score (Index of MulKple DeprivaKon 2010) was used to assess geographical deprivaKon for 152 PCOs; a lower rank indicates a higher deprivaKon. LogisKc regression was used to determine correlaKon between social deprivaKon and access to CRT. Results were considered significant at p<0.05.

Results: Complete sets of data were available for 137/152 (88%) of the PCOs. Across London there was a 11-­‐fold difference in adjusted CRT implant rates between the lowest and highest PCO. LogisKc regression (Figure 1) demonstrated a strong correlaKon between the social deprivaKon average score rank and adjusted implant rate (r2=0.2091, p=0.01).

Conclusions: PaKents with heart failure living in London from socially deprived areas are less likely to receive a CRT implant. However, across England and across urban areas, social deprivaKon does not predict access to treatment. Strategies to improve access to heart failure and arrhythmia specialists should be targeted towards deprived geographical areas in London. The reasons for variaKon in implant rates naKonwide remain unclear.

Figure 1: Across England there was a 17-­‐fold difference in CRT implant rate adjusted for emergency heart failure admissions between the lowest and highest PCO.

29

Figure 2: Logis;c regression demonstrated no correla;on between the social depriva;on average score rank and adjusted implant rate (r2=0.0081, p=0.27)

30

POSTER PRESENTATIONS P1 – A REVIEW OF IN-­‐PATIENT HEART FAILURE MANAGEMENT BETWEEN CARDIOLOGIST AND NON-­‐CARDIOLOGISTS: THE GOOD, THE BAD AND THE AVERAGE LENGTH OF STAY Jordan M, Skingle A, Wa\s-­‐Cherry R.

Background: Mortality and morbidity following admission for acute heart failure (AHF) are significant, with 11% of paKents likely to die in hospital. Growing evidence suggests that mortality can be reduced if paKents are rapidly and accurately assessed in the Emergency Department, and admi\ed to a cardiology ward with experKse in the management of acute and chronic heart failure. McDonagh et al reported a significant difference in mortality rates among paKents treated on a cardiology (7.8%) vs general-­‐medicine ward (13.2%).

Mortality and morbidity in paKents with AHF are also influenced by prescripKon rates of common cardiac medicaKons. These rates vary between cardiology wards and general medical wards. PaKents with LVSD treated in cardiology units were twice as likely to be discharged on beta blockers as those treated in general wards, and also more likely to go home on ACEI/ARB and mineralocorKcoid receptor antagonist (MRA).

Methods: We present data collected at Wrexham Maelor Hospital over 6 months, analysing differences between cardiologists and non-­‐cardiologists in duraKon of hospital stay and heart failure medicaKons prescribed at discharged, in paKents with a confirmed diagnosis of heart failure.

Results: A total of 131 paKents were included in the study. 49 paKents (41.2%) were admi\ed with symptoms of acute heart failure under the cardiology team compared with 70 paKents (58.8%) who were cared for by general medical teams.

Of the 49 paKents admi\ed under the care of a cardiology consultants, 28 paKents (57.1%) were discharged within 5 days or less and only 8 paKents (15%) required admission beyond 15 days. Conversely, in the cohort of 70 paKents admi\ed under general physicians, only 9 paKents (13%) were successfully discharged afer 5 days or less with 40 paKents (57%) remaining in hospital for 16 days or more. AddiKonally, 14 paKents (20%) were admi\ed for 40 days or more.

Afer review by a cardiologist 24 paKents (49%) were discharged home on an ACEi, 40 paKents (82%) on a beta blocker and 31 paKents (63%) on a MRA, conversely, afer discharge by a general physician, 20 paKents (29%) were on an ACEi, 41 paKents (59%) on a beta blocker and 25 paKents (36%) on a MRA. 12 new paKents were discharged on triple therapy of which the cardiology team reviewed 9 and general medical teams reviewed 3.

Conclusion: PaKents admi\ed to a specialist cardiology ward with AHF are more likely to be discharged earlier and on the correct cardiac medicaKons than paKents admi\ed with the same diagnosis to general medical wards. A service which focuses on early cardiology review of paKents presenKng with AHF and iniKal management on a specialist cardiac ward will improve paKent care and reduce length of stay. However, there is sKll room for improvement, even from the specialists!

31

P2 – AN AUDIT OF THE PRESCRIPTION AND DELIVERY OF ANTIBIOTIC PROPHYLAXIS IN IMPLANTABLE CARDIAC ELECTRONIC DEVICE INSERTIONS IN ACUTE CARDIOLOGY

Wong J.

Over 25,000 implantable cardiac electronic devices (ICED) are inserted in the UK each year with costs exceeding £43million. Recent data shows a rising rate of ICED infecKons disproporKonately to the rate of inserKon. ICED related infecKons can lead to complicaKons resulKng in increased cost and worse outcomes, especially with ICED related endocardiKs which has a mortality rate of 27%. Evidence recommends pre-­‐inserKon systemic anKbioKc prophylaxis, however there has been uncertainty on the anKbioKc choice. The BriKsh Society for AnKmicrobial Chemotherapy (BSAC) recently published guidelines recommending Teicoplanin as the systemic anKbioKc prophylaxis of choice over Flucloxacillin, the current most used prophylaxis for ICED. We wanted to assess and improve compliance of local ICED guidelines and explore applicability of BSAC guidelines.

The standard used was local ICED guidelines which recommend co-­‐amoxiclav for non-­‐penicillin allergic paKents and Teicoplanin with Gentamicin for penicillin allergic paKents. The audit looked retrospecKvely at paKents who underwent ICED inserKon as an acute procedure in a 6 month period and areas where pracKse was not compliant idenKfied. Improvement of compliance involved a paKent pathway policy change and a re-­‐audit was done in order determine improvements.

29 paKents were idenKfied undergoing acute ICED inserKon between July and November 2013. 26 (89%) prescripKons followed protocol. There were records of prophylaxis administraKon Kme and procedure start Kme in 15 paKents. 7 (53%) was within the 1hr target of administering prophylaxis before inserKon. The mean latency was 80min with a range of 260min. During the re-­‐audit 12 paKents were idenKfied between May and July 2014. 12 (100%) prescripKons followed protocol. 10 paKents had latency recorded, 6 (60%) were within the 1hr target. The mean latency between the administraKon of prophylaxis and procedure start Kme was 56min with a range of 120min.

There were high compliance rates in the type of anKbioKcs with the errors being in the penicillin-­‐allergic protocol which resolved with successful staff educaKon.

Co-­‐amoxiclav has good acKvity against CoNS and OSSA; the main organisms causing infecKon, however it only has a half-­‐life of 1hr afer which infecKon rates rise. The paKent pathway was for the administraKon of prophylaxis on the ward before transfer to the catheterizaKon laboratory and this caused latency. Change to administering in the catheterizaKon laboratory resulted in a decrease in mean latency to within the 1hr. The range between prophylaxis administraKon and the procedure start Kme decreased by 140min. However 40% of paKents were sKll exceeding the 1hr target, this gives greater jusKficaKon for the adopKon of BSAC recommendaKons due to the much longer half-­‐life of Teicoplanin as well as addressing the rising resistance rates within CoNS and allowing the same protocol regardless of penicillin allergies.

32

P3 – OPTICAL COHERENCE TOMOGRAPHY (OCT): AN EXPERIMENTAL VALIDATION FOR VASCULAR IMAGING Aung HT .

Background: OpKcal Coherence tomography (OCT) is a novel light based imaging method and intra-­‐vascular catheter-­‐ based OCT is an exciKng development for intra-­‐coronary imaging within human blood vessels in vivo. OCT will be used in the first-­‐in-­‐human trial called PROTECT trial (Gene Therapy to Protect from Saphenous Vein Graf Failure).

This study aims to validate the measurement accuracy and sensiKvity of OCT.

Methods: Three phantom tubes with a plaque-­‐like bump lesion to mimic human stenosed vessels designed by NHS Medical Physics were imaged as well as three cadaveric saphenous veins and 1 porcine coronary artery which were obtained from the University of Glasgow Anatomy Department and Sho\s abba\oir, respecKvely. All the grafs were imaged with OCT (ILUMIEN OPTIS, St. Jude Medical) and compared with current gold standard, intravascular ultrasound (IVUS, Boston ScienKfic)) and photomicroscopy laboratory reference method (NHS Pathology, New South Hospital, Glasgow). We have created our own measurement sofware, iScan (NHS Medical Physics) to overcome the theoreKcal limitaKons for depth of field due to light a\enuaKon of the commercial sofware package imaging techniques (both OCT and IVUS). All the methods were compared with laboratory photomicroscopy and they are also compared against each other.

Results: There was a strongest posiKve linear correlaKon between OCT and photomicroscopy lumen diameter measurements with r=-­‐0.88; (p<0.01) compared to IVUS (r=0.83) and iScan(r=0.51). IVUS showed the best wall thickness measurement with the least difference from photomicroscopy with 288.72% followed by OCT with 312.76% and iScan with 420.87%.

Conclusions: OCT, IVUS and iScan each play an important potenKal diagnosKc uKlity role in intravascular imaging measurements. As far as PROTECT trial is concerned,OCT with further improvement in iScan is valid to use for the most accurate measurements of image analysis in PROTECT.

P4 – EVALUATION OF CARDIOLOGY OUTPATIENT REFERRALS AT THE UNIVERSITY HOSPITAL OF WALES WITH A VIEW TO DEVELOPING PROTOCOL-­‐DRIVEN SPECIALITY CLINICS

Luk E, Upadhyaya C, Wheeler R.

Background: To evaluate cardiology outpaKent referrals in order to streamline the current referral process and to idenKfy possible areas for service improvement.

Methods: Pro-­‐formas designed by a cardiology registrar and me were used to assess whether referral le\ers from clinicians and general pracKKoners (GPs) met the criteria for cardiology outpaKent referrals. Data was collected from Medical Records at University Hospital Wales (UHW) daKng from March to June 2014.

Results: 374 paKents’ data was collected and analysed. Chest pain consKtutes the majority of cardiology outpaKent referrals (33%), followed by palpitaKons (28%). Heart failure and valvular heart disease form 13% and 9% of the referrals respecKvely, while 17% of referrals fall into the miscellaneous category.

Conclusions: Data collected is reflecKve of poor referral le\er quality. It stresses the need to review the current referral system to enhance efficiency in delivering cardiac care at UHW. It also points towards making cardiology diagnosKcs more readily accessible to GPs.

33

P5 -­‐ SYNCOPE MANAGEMENT AT EMERGENCY DEPARTMENT IN SINGAPORE: A RETROSPECTIVE STUDY Tan YQ

Background: Syncope, defined as transient loss of consciousness due to global cerebral hypoperfusion and characterized by rapid onset, short duraKon and spontaneous complete recovery, is extremely common in the general populaKon. However, there is very limited data about syncope in Asia. This retrospecKve study aims to invesKgate the incidence and management of paKents presenKng with syncope at the emergency department (EMD) of an academic medical centre, NaKonal University Hospital (NUH) in Singapore.

Method: PaKents presenKng to the NUH EMD between January 2012 to July 2012 with syncope will be idenKfied from EMD clinical databases by searching for the following admission ICD codes 992.1 (Heat Syncope), 780.2 (Syncope and collapse), 337.1 (CaroKd sinus syndrome) and 458.0 (OrthostaKc hypotension). Progress was assessed by review of electronic case records.

For each paKent, the following baseline characterisKcs would be recorded; age, sex, ethnicity, number of syncopal events in the prior 12 months, circumstances prior to syncope, prodromal symptoms, duraKon of syncope, recovery from syncope, past medical history, medicaKon history, family history of sudden death, 12 lead ECG, rouKne blood tests, physical examinaKon and duraKon of hospitalisaKon.

Results: Out of 659 paKents idenKfied, 408 presented with an episode of true syncope involving transient loss of consciousness and were analyzed. 105 of 408 had no past medical history, had normal physical examinaKon and baseline tests (FBC, 12 lead ECG and renal panel). 56% of them were discharged at EMD, with only 46% of those paKents having a definiKve diagnosis. 233 paKents were admi\ed with a mean length of stay of 2.6 ± 0.32 days (range 1 to 17). AddiKonal tests (electroencephalograms, telemetry, CT brain, 2D echography and cardiac catheterizaKon) were performed on 41% of them, of which 47% of those paKents received a definiKve diagnosis from the tests. 6.3% of the all paKents presenKng to EMD, whether discharged at EMD or admi\ed for further invesKgaKons, returned to the EMD within a year for syncope and almost all of them did not receive a definiKve diagnosis during last presentaKon.

Conclusions: Syncope is responsible for a significant number of EMD and hospital admissions in Singapore. The diagnosKc yield from current pracKces is less than 50% despite the use of numerous invesKgaKons and more than half of the paKents being admi\ed from EMD. The introducKon of an dedicated syncope care pathway may improve clinical outcomes and improve cost-­‐effecKveness.

34

P6 -­‐ THE USE OF HIGH-­‐SENSITIVITY TROPONIN IN THE DETERMINATION OF HEALTH OUTCOMES Noaman A.

Background: High-­‐sensiKvity troponin assays are able to idenKfy paKents with non-­‐specific myocardial injury and have been correlated with prognosKc outcome. Currently, li\le is known about the incidence of myocardial injury and what it means in the emergency department.

Aims: To evaluate the characterisKcs and outcome of consecuKve paKents presenKng to the emergency department straKfied against admission troponin.

Methods: ConsecuKve paKents presenKng to the emergency department were idenKfied over a period of 10 days.

Where a blood sample was taken, troponin was quanKfied with a hsTnI assay. PaKents with clinically requested troponin were excluded.

Results: PaKents with the highest troponin levels were older, more likely to suffer atheroscleroKc disease, possess more cardiac risk factors, have undergone past revascularisaKon, and display more adverse physiological parameters, biochemistry, renal funcKon and electrocardiographic changes (p<0.001). The 99th percenKle value for our emergency department populaKon was 677 ng/L (90% CI 449-­‐1377). For every doubling of troponin, risk of death increased by 35% (RR 1.350, 95% CI 1.196-­‐1.525) afer appropriate risk straKficaKon.

Conclusion: Cardiac troponin appears to be a significant independent marker of morbidity and mortality in paKents presenKng to the emergency department, independent of presenKng complaint.

P7 – HIGH-­‐SENSITIVITY CARDIAC TROPONIN AND ITS CLINICAL USE: A GENDER BASED ANALYSIS

Vaswani A.

Background: Lowering the diagnosKc threshold for the diagnosis of myocardial infarcKon using a high sensiKvity cardiac troponin I assay with sex-­‐specific cut-­‐offs is controversial. Whilst high sensiKvity assays may improve diagnosKc sensiKvity for type I myocardial infarcKon, it is likely to affect clinical specificity. We evaluated the prevalence of myocardial injury in consecuKve paKents presenKng to the emergency department in men and women.

Methods: All consecuKve paKents who presented to the emergency department were idenKfied over a 10 day period from July 5th to July 16th 2013 and had their high sensiKvity troponin measured. Troponin results were not used in clinical decision making. Electronic paKent records were used to collect baseline clinical informaKon and outcomes.

Results: Over a period of 10 days, (n=1054) paKents were recruited. Of these, (n=918, 46% men) did not have clinically requested troponin. The median hs-­‐TnI values for men were 4ng/L, with an IQR of 2-­‐11, and for women, 3ng/L, and an IQR of 1-­‐7. Men were more likely to have a previous history of atheroscleroKc disease, smoking and be treated medically or have undergone procedures. Men who had a posiKve hs-­‐TnI were also more likely to present with chest pain on admission.

Conclusion: Our findings support establish data that men were more likely to present with previous heart disease, risk factors, comorbidiKes and a history of previous revascularisaKon than women, and were also more likely to be undergoing treatment. Troponin is also an important prognosKc marker, indicaKng greater morbidity and mortality irrespecKve of gender.

35

P8 -­‐ HAEMODYNAMIC MECHANISMS UNDERLYING ESSENTIAL HYPERTENSION CHANGE ACROSS THE ADULT AGE-­‐SPAN: THE ANGLO-­‐CARDIFF COLLABORATIVE TRIAL Coumbe B, McEniery C, Maki-­‐Petaja K, Wlikinson I.

Background: EssenKal hypertension is a common condiKon and a major modifiable risk factor for cardiovascular disease. Although ofen viewed as a uniform condiKon, essenKal hypertension encompasses a number of disKnct pa\erns of blood pressure (BP) elevaKon, the prevalence of which appears to vary with age. We hypothesized that different haemodynamic mechanisms account for age-­‐related differences in BP phenotypes and our aim was to test this hypothesis in a large sample of individuals covering the adult age-­‐span.

Methods: Detailed haemodynamic data including seated (clinic) BP, cardiac output (CO) and stroke volume (SV), peripheral vascular resistance (PVR) and aorKc pulse wave velocity (aPWV), a robust measure of aorKc sKffness, were available in 5337 individuals (2381 males), aged between 18-­‐92 years. All individuals were free of cardiovascular disease and medicaKon. Data was straKfied according to age, gender and BP phenotype, on the basis of clinic BP, as follows: normotensive (NT), isolated systolic hypertension (ISH), systolic diastolic hypertension (SDH) and isolated diastolic hypertension (IDH). Significance was determined using one-­‐way ANOVA (P<0.05).

Results: The analysis confirmed previous findings regarding the distribuKon of hypertensive phenotypes across the adult life span with ISH being predominant in younger and older individuals and SDH being predominant in middle aged individuals. Within the younger populaKon there was a preponderance of males over females in ISH paKents (11:1), a\ributed to elevated CO and SV, confirming our previous findings. In females SDH and IDH were more common and associated with elevated PVR and aorKc sKffness. However, within the female ISH populaKon there was an unusual phenotype with elevated cardiac output afer correcKon for BMI and heart rate (NT: 6.58±1.50 ISH: 9.32±3.13, P<0.001). In individuals over 60 the most common hypertensive phenotypes in males and females was ISH. In contrast to their younger counterparts there was no bias towards men present in older ISH paKents (1:1).

Older ISH paKents were characterised by markedly elevated aPWV compared with NTs (F: NT:8.24±1.88, ISH: 9.78±2.22, P<0.001 and M: NT:8.68±2.06, ISH: 10.08±2.47, P=0.007).

Conclusion: The prevalence of different BP phenotypes varied across the adult age span in males and females were associated with disKnct haemodynamic pa\erns. This data suggests that physiological profiling and targeKng therapy towards the underlying haemodynamic abnormality may be a worthwhile strategy with which to be\er idenKfy and intervene on this important risk factor.

P9 -­‐ FAMILIAL THORACIC AORTIC ANEURYSM SYNDROME Iakovlev E, Iakovlev V, Erre\ L.

Background: The majority of thoracic aorKc aneurysms in young paKents are as a result of familial syndromes. These aneurysms are usually asymptomaKc and carry a high risk for dissecKon and rupture. The pathogenesis of familial aorKc aneurysm syndrome is poorly understood and looked into here.

Aims: To invesKgate the effects of CO on human pulmonary artery vascular smooth muscle cell (hPASMC) proliferaKon. We hypothesised that CO may exert anK-­‐proliferaKve effects via inhibiKon of T-­‐type Ca2+ channels.

Methods: A case of a familial thoracic aorKc aneurysm was reviewed in combinaKon with published literature.

Results: We present a case of a 20-­‐year-­‐old male with an ascending thoracic aorKc aneurysm. He has a posiKve family history of aorKc dissecKon with his father having been operated on a few weeks prior. Both the paKent and his father have no Marfanoid features. Imaging studies in the paKent showed a dilated ascending aorta and mild aorKc insufficiency due to a bicuspid valve. His complaints were that of chest pain and shortness of breath. Afer undergoing an elecKve graf repair, the excised aorta was sent to pathology. The excised aorta showed an old dissecKon with necrosis and resorpKon of the inner half of the aorKc wall and a diverKculum-­‐like dilataKon of the remaining outer half. Microscopically it showed cysKc medial necrosis of the media. Through case reports and outside literature, the geneKcs and pathogenesis of familial thoracic aorKc aneurysm syndrome is discussed.

Conclusion: More research is needed to understand the pathogenesis of familial thoracic aorKc aneurysm syndrome and to develop strategies in the management of these paKents.

36

P10 -­‐ MEDIASTINAL CYSTS MIMICKING PERICARDITIS Iakovlev E, Iakovlev V, Erre\ L, Siddiqui R.

IntroducHon: A case of constricKve pericardiKs with concurrent mediasKnal cyst has been reviewed in combinaKon with published literature. MediasKnal cysts are relaKvely rare and can be overlooked in a work up for mediasKnal condiKons, yet they may present a diagnosKc challenge both clinically and histologically. They can have a variable radiological appearance and mimic other condiKons.

Methods/Results: We present a case of a 58-­‐year-­‐old male with two-­‐year history of chest pain and dyspnea. On assessment he was found to have right-­‐sided heart failure, pericardial effusion and other findings in keeping with constricKve pericardiKs. The treatment team proceeded with pericardectomy, during which an anterior mediasKnal mass was also found. Histologically, the pericardium was fibrosed and thickened confirming constricKve pericardiKs. The anterior mediasKnal mass was a separate simple cyst lined by respiratory epithelium. The diagnosis was constricKve pericardiKs with concurrent foregut-­‐bronchial cyst. Although, in this case the two condiKons appeared coincidental, an anatomical or pathophysiological connecKon cannot be excluded for all cases. Notably, the cyst was not visualized radiologically, likely obscured by the pericardiKs and effusion. We searched published literature, which includes several reports of mediasKnal cysts misdiagnosed preoperaKvely, in order to analyse diagnosKc approaches between mediasKnal cysts and the condiKons they can mimic. The management of these lesions was also analysed.

Conclusions: MediasKnal cysts should be included in the differenKal diagnosis for paKents with clinical signs of mediasKnal condiKons.

P11 -­‐ CONSENT FOR CRT DEVICE IMPLANTATION: ARE WE GIVING PATIENTS ACCURATE INFORMATION? Henery R.

Background: Cardiac-­‐resynchronisaKon therapy (CRT) is becoming an increasingly important therapeuKc opKon for paKents with moderate to severe heart failure. However, there are several complicaKons associated with CRT implant, including pneumothorax, lead reposiKoning, and failed implantaKon. For paKents to give informed consent to this procedure, they must be given accurate informaKon regarding potenKal complicaKons.

The aim of this audit was to establish what informaKon operators at terKary referral centres currently give to paKents when they are consented for CRT implant, and to compare this with the actual complicaKon rates during one calendar year.

Methods: This was a retrospecKve audit and data was obtained from the health record department on paKents implanted with a CRT device during the calendar year 2012. A proforma was created to record baseline characterisKcs, operaKon details and post-­‐operaKve complicaKons for each paKent. A quesKonnaire was also completed by five operators and returned for data analysis.

Results: In the audit cohort of 104 paKents, there were 40 recorded major complicaKons in 35 paKents. This gave an overall complicaKon rate of 33.7%, over six Kmes higher than the rate quoted by operators when they consent paKents for CRT implant. 12.5% of paKents later required lead reposiKoning, a rate 12 Kmes higher than the rate quoted by one operator. Pneumothorax occurred at a rate of 5.8%, nearly six Kmes higher than the rate quoted by operators.

There was failure to place a lef ventricular pacing lead in 6.7% of paKents. There was discordance in the rates of failed implantaKon quoted by operators: two quote a rate six Kmes lower than the observed rate, whilst one quotes a rate of 5%, only slightly lower than the observed rate. The other two operators do not specifically inform paKents of the rate of failed implantaKon.

Conclusion: This audit highlighted that certain complicaKons related to CRT implant are occurring at rates higher than those reported to paKents, parKcularly lead reposiKoning and pneumothorax. There is also variability in reporKng amongst operators, both in which complicaKons are reported and in their rates of occurrence. To address these issues, there are plans for a wri\en consent form with complicaKon rates to be viewed at the pre-­‐assessment 37 clinic. However, there will also be an ongoing audit of CRT complicaKons to capture the informaKon more accurately.

P12 -­‐ NCVD-­‐PCI REGISTRY : RETROSPECTIVE COHORT STUDY COMPARING DOUBLE VERSUS SINGLE STENTING IN TRUE BIFURCATION LESIONS OF DISTAL LEFT MAIN STEM CORONARY ARTERY DISEASE Ang BH, Chin KP, Tan DWJ, Chan CC, Chee KH.

IntroducHon: Coronary bifurcaKon lesions are frequently encountered and the best intervenKon strategy draws a lots of interests and have been a subject of intense therapeuKc discussions. Although provisional stenKng technique being well accepted, there is sKll no indexed treatment for bifurcaKon lesions and dual-­‐stent technique has been proven to be as efficient in some cases.

Aims: This study holds the objecKve of looking into current choice of treatment in clinical pracKce, to further assess the necessity and outcome of dual-­‐stent strategy comparing to one-­‐stent technique group.

Methods: The data was extracted from Malaysia NCVD-­‐PCI registry. The studied populaKon comprised of 90 paKents who underwent PCI on LMS at NaKonal Heart InsKtute Malaysia between years 2007 to 2010. PaKents were idenKfied afer viewing of respecKve angiographies, only true bifurcaKons lesions are recorded together with the choice of stent strategy. Follow up data was recorded at six month and one year post intervenKon based on paKents’ scheduled visit to cardiologist. PaKents’ outcomes, follow up details, various clinical condiKons were extracted from the medical records provided by NaKonal Heart InsKtute.

Results: From the total of 90 paKents, one-­‐stent group comprises 62 paKents (68.9%) and mulKple-­‐stent group with 28 paKents (31.1%). 51.4% of the distal involvement lesions have lesions at distal lef main stem plus 2 or 3 branches while 24.3 % was from distal lef main plus 1 branch. In one-­‐stent group, the most used technique was simple cross over with 47.8% while the most used mulKple stenKng technique was crush technique with 8.9% of all PCI done.

Majority of paKents have extension of coronary artery disease either the lef anterior descending artery (83.3%) and lef circumflex artery (74.4%). Clinical outcome recorded at 3 stages; post-­‐procedural, 6 months follow up and one year follow up shows no staKsKcal difference (p-­‐value > 0.05) for both one stent and mulKple stent group.

Conclusions: One-­‐stent strategy and dual-­‐stent strategy do not affect the paKents’ immediate and long term outcome, therefore there is no necessity of using dual-­‐stenKng techniques when not indicated.

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P13 -­‐ SUBLINGUAL GLYCERYL TRINITRATE USE AMONG PATIENTS WITH CORONARY HEART DISEASE AND CALLING FOR HELP DURING CHEST PAIN EXPLORING MEDICINES-­‐ TAKING BEHAVIOUR Giannoudi M, Abdul-­‐Raman D, KhaKb R, Hall A.

Background: GTN is prescribed to prevent or relieve CP among paKents with established coronary heart disease (CHD). It is also a useful prompt for paKents to call 999 if pain persists despite GTN administraKon within certain Kmeframe. The NaKonal InsKtute of Health and Care Excellence (NICE) recommends a Kme frame of 10 minutes. We explored GTN use to establish how effecKve knowledge of the rule had been in helping paKents call for help.

Method: Using a quesKonnaire, we examined: how long the paKent waited before calling for help afer the onset of CP, use of GTN at that episode, normal use of GTN in managing their angina, and knowledge of the GTN rule.

ConsecuKve paKents presenKng to cardiology wards were interviewed based on three inclusion criteria: paKent had established CHD, was admi\ed to hospital with CP and had a GTN prescripKon before admission. The ‘EPRO’ database system was used to obtain the paKent’s final diagnosis.

Results: 35 paKents (27 male and 8 females) parKcipated. 63% used GTN prior to admission. The average Kme from onset of symptoms to calling 999 (S-­‐C Kme) was 116min (± 315). Only 43% of all paKents were aware of the GTN rule. Of the 20 paKents who were not aware of the rule, 80% said that a healthcare professional (HCP) advised them in the past on GTN use. The most common reason for not using GTN was avoiding side effects. More paKents who knew the GTN rule used GTN (p > 0.05), as were those with a previous CP admission (p = 0.001) and those who used GTN at a prior admission (p <0.001). PaKents who do not usually need to use their GTN (stable) were less likely to use it during an acute episode of CP (p < 0.001).

The mean S-­‐C Kme was lower among paKents who knew the GTN rule compared to those who did not (31min ± 60 vs. 183min ± 410 respecKvely, p > 0.05). Women waited less than men, but were less likely to use GTN. The mere advice by HCPs did not reduce mean S-­‐C Kme. PaKents with ST elevaKon MI almost instantly called 999, however those with non-­‐ST elevaKon MI waited (on average) 138min. Of the 15 paKents with final diagnosis of non ST-­‐ elevaKon acute coronary syndrome (NSTACS), 75% used GTN to manage their angina, but only 40% used GTN before admission and 33% were aware of the GTN rule.

Conclusion: Our data shows that paKents with chest pain are waiKng too long before calling 999. While the use of GTN during acute CP should help guide paKents on when to call for help, many are not using GTN and lack awareness of a Kme frame (10-­‐minute rule) which possibly further delays the S-­‐C Kme. As the mere advice on the use of GTN by HCPs did not yield shorter waiKng Kmes, the informaKon provided should be\er emphasise the 10-­‐ minute rule and explore paKents’ concerns about side effects. Advice should also be targeted more at males, and those with stable CHD who have not had recent admissions. The small sample possibly weakened the staKsKcal power of the findings.

P14 -­‐ OPTICAL COHERENCE TOMOGRAPHY (OCT): AN EXPERIMENTAL VALIDATION FOR VASCULAR IMAGING Aung HT.

Background: OpKcal Coherence tomography (OCT) is a novel light based imaging method and intra-­‐vascular catheter-­‐based OCT is an exciKng development for intra-­‐coronary imaging within human blood vessels in vivo. OCT will be used in the first-­‐in-­‐human trial called PROTECT trial (Gene Therapy to Protect from Saphenous Vein Graf Failure). This study aims to validate the measurement accuracy and sensiKvity of OCT.

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Methods: Three phantom tubes with a plaque-­‐like bump lesion to mimic human stenosed vessels designed by NHS Medical Physics were imaged as well as three cadaveric saphenous veins and 1 porcine coronary artery which were obtained from the University of Glasgow Anatomy Department and Sho\s abba\oir, respecKvely. All the grafs were imaged with OCT (ILUMIEN OPTIS, St. Jude Medical) and compared with current gold standard, intravascular ultrasound (IVUS, Boston ScienKfic)) and photomicroscopy laboratory reference method (NHS Pathology, New South Hospital, Glasgow). We have created our own measurement sofware, iScan (NHS Medical Physics) to overcome the theoreKcal limitaKons for depth of field due to light a\enuaKon of the commercial sofware package imaging techniques (both OCT and IVUS). All the methods were compared with laboratory photomicroscopy and they are also compared against each other.

Results: There was a strongest posiKve linear correlaKon between OCT and photomicroscopy lumen diameter measurements with r=-­‐0.88; (p<0.01) compared to IVUS (r=0.83) and iScan(r=0.51). IVUS showed the best wall thickness measurement with the least difference from photomicroscopy with 288.72% followed by OCT with 312.76% and iScan with 420.87%.

Conclusions: OCT, IVUS and iScan each play an important potenKal diagnosKc uKlity role in intravascular imaging measurements. As far as PROTECT trial is concerned,OCT with further improvement in iScan is valid to use for the most accurate measurements of image analysis in PROTECT.

P15 -­‐ A COMPARISON OF IN-HOSPITAL LENGTH OF STAY BETWEEN TRANSCATHETER AORTIC VALVE IMPLANTATION AND HIGH-RISK SURGICAL AORTIC VALVE REPLACEMENT

OPTIMISATION IN NHS HEALTH CHECKS: BLOOD PRESSURE AND DIABETES RISK Cockburn H.

Background: AorKc Stenosis is a degeneraKve disease of the aorKc valve causing it to narrow. The convenKonal treatment for severe aorKc stenosis is surgical aorKc valve replacement (AVR). However, as aorKc stenosis is largely a disease of ageing, paKents are ofen considered inoperable or too high risk for convenKonal AVR so transcatheter aorKc valve implantaKon (TAVI) may be considered at the Edinburgh Royal Infirmary.

Aims: To prove that length of stay (LOS) is longer for paKents who have high-­‐risk surgical AVR compared to paKents who have TAVI. This study eliminated the variables of age and gender as they do not affect LOS and therefore a valid conclusion could be reached. The in-­‐hospital LOS was calculated for 94 TAVI and 39 high-­‐risk surgical AVR paKents.

Research: The age composiKon of TAVI paKents and AVR paKents was compared and the difference in median age was calculated. For each operaKon, the paKents were divided into female and male gender to calculate the median LOS for each.

The TAVI procedure was broken down into method of valve delivery: transfemoral or transaorKc/transapical and the median LOS for each group was calculated.

Trends in gender and age where determined within TAVI and AVR groups individually.

The effect of age and gender on LOS of all the paKents was studied to prove that these variables do not influence LOS. This allowed a reliable comparison of LOS between the TAVI and AVR operaKon. Age is a conKnuous variable therefore a correlaKon coefficient was calculated to see if there is a trend between age and LOS. The difference in mean LOS for females and males was calculated. A comparison of LOS between the TAVI and AVR operaKons could then be made.

Conclusions: TAVI paKents were likely to be older than high-­‐risk surgical AVR paKents by a mean age of 5 years.

Within the TAVI populaKon, the transaorKc/transapical approach resulted in a longer LOS compared to the transfemoral route by a median of 1.5 days. Age impacts TAVI LOS; as age increases, the LOS also increases.

Looking at the age and gender distribuKon for the data as a whole, it was found these variables do not contribute to the LOS. A reliable conclusion could be made between the two procedures. In conclusion, the length of stay for TAVI was less compared to paKents who had high-­‐risk surgical AVR by a median of 4 days and a mean of 5.11 days.

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P16 -­‐ DOES CHEMOTHERAPY HAVE TO BE HEART-­‐BREAKING? Sawways J, Trafford A.

IntroducHon: Many people are treated with anK-­‐cancer drugs, several of which can induce cardiac-­‐dysfuncKon causing debilitaKng and life-­‐shortening condiKons. The class of anK-­‐cancer drugs, checkpoint kinase inhibitors’ (ChKIs) development has slowed due to cardiotoxicity observed during clinical trials. This study aims to improve the mechanisKc understanding of the cardiotoxicity exhibited, which could lead to redesigns of ChKIs and a reducKon of cardiotoxicity in cancer paKents.

Methods: Isolated rat ventricular cardiomyocytes loaded with a calcium sensiKve indicator were sKmulated and calcium transients were recorded. During recording, cells were superfused sequenKally with a control soluKon (2 minutes), ChKI soluKon (2 minutes) and control soluKon again (2 minutes). 6 ChKIs were used (AZD7762 and 5 novel anonymous ChKIs). The magnitude and rate of decay of calcium transients were compared between groups and significance was assessed using the repeated measures ANOVA rank test.

Results: a) Calcium transient magnitude: There were no significant differences between the control, drug and washout for AZD7762 and drugs 1-­‐3. Drugs 3-­‐5 all showed no significant differences between control and drug, but the washout was significantly decreased (P=0.001, 0.006 and 0.002 respecKvely). b) Calcium transient rate of decay: There were no significant difference between the control, drug and washout for AZD7762 and drugs 1-­‐4, but drug 5 showed a significant decrease in the drug and increased in the washout compared to the control (P=0.002).

Conclusion: The inconsistent results suggest ChKIs do not have a class-­‐wide effect on calcium cycling. Further work into alternate mechanisms of ChKIs induced cardiotoxicity is needed.

P17 -­‐ GENETIC AND NON-­‐GENETIC RISK FACTORS FOR STATIN-­‐INDUCED MYOPATHY Shakoor Z.

IntroducHon: Since their introducKon in 1987 staKns have revoluKonized the treatment of hypercholesterolemia (Law et al., 2006). Although they are generally well tolerated around 13% of paKents are thought to experience myopathy as an adverse effect, which can result in rhabdomyolysis.

Methods: A literature search was performed using the terms “staKn” and “myopathy” to search various databases.

An inclusion and exclusion criteria was subsequently applied to achieve a manageable number of arKcles for inspecKon to determine their suitability.

Results: PharmacogeneKcs: A genome wide associaKon study (GWAS) concluded that there was an increased risk of simvastaKn-­‐induced myopathy in carriers of SLCO1B1 gene polymorphisms. The SEARCH study also confirmed evidence for the role of the SLCO1B1*5 variant in inducing staKn intolerance in atorvastaKn treated paKents (Link et al., 2008; Voora et al., 2008).

Non-­‐geneKc risk factors: Age and staKn dose have been idenKfied as major risk factors for SIM (Shepherd et al., 2002; Baer et al., 2007).

There are mulKple confounding factors such as poly-­‐pharmacy, renal, hepaKc, or mulKsystem disease which may coincide with increasing age can result in adverse effects such as SIM. Generally being female, exercising, taking mulKple medicaKons and an excessive alcohol intake will increase the risk of myopathy (Fa•nger et al., 2000; Bhardwaj et al., 2013; Thompson et al., 2013; Giannoglou et al., 2007). The risk of SIM also varies depending on the staKn used.

Conclusion: An appreciaKon of factors affecKng SIM can have powerful implicaKons, especially if geneKc and non-­‐ geneKc risk factors are combined to calculate an overall risk of myopathy. Devising a predicKve model as in the case of Abacavir and Warfarin could prove extremely valuable for the safer prescripKon of staKns. In the meanKme perhaps the first steps are to publish guidelines on the implementaKon of pre-­‐treatment geneKc screening prior to staKn use as there is no guidance from bodies such as the Medicines and Healthcare products Regulatory Authority (MHRA) currently available.

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P18 – SEARCHING FOR INHERENT SUSCEPTIBILITY TO VENTRICULAR ARRHYTHMIAS IN YOUNG UNTRAINED PLAKO +/-­‐ HEARTS Osbourne B.

IntroducHon: The inheritable disease Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) frequently causes ventricular tachyarrhythmias, and sudden death, in young athletes. MutaKons in desmosomal proteins (e.g. plakoglobin) cause ARVC and increased ventricular arrhythmia inducibility in aged/trained mice but remains untested in naïve hearts. We invesKgated ventricular arrhythmia (>1 second) suscepKbility in young, untrained mice heterozygous for plakoglobin (Plako+/-­‐) compared to WT, and whether epicardial pacing or Na+ channel blockade alters electrophysiological parameters.

Method: 44 hearts (37 male, 7 female; 7-­‐23 weeks) were rapidly excised and perfused with Krebs-­‐Henseleit soluKon on a Langendorff apparatus. Monophasic acKon potenKals recorded from the ventricles provided measurements of acKvaKon Kmes (AT) and acKon potenKal duraKons during right ventricular endocardial pacing with an octapolar catheter. EffecKve refractory periods were elucidated by premature extrasKmuli afer an 8-­‐pulse S1 train. Flecainide infusion (500nM) and epicardial pacing a\empted to exaggerate potenKal conducKon defects. Values stated as mean ±SEM.

Results: Plako+/-­‐ hearts were not more suscepKble to ventricular arrhythmias (WT: 3/12, Plako+/-­‐: 4/10) and electrophysiological parameters were equivalent between genotypes. Epicardial pacing more strongly affected the mean right ventricular AT in Plako+/-­‐ hearts (Endocardial: 7.50±1.90, Epicardial: 12.38±0.73) than WT (Endocardial: 8.10±0.96, Epicardial: 10.30±1.07) although neither result was significant. Flecainide-­‐induced AT prolongaKon was apparent afer 10 minutes infusion for both genotypes but only significant for WT (Before: 10.30±1.07, Flecainide: 14.81±1.15; Plako+/-­‐ Before: 12.38±0.73, Flecainide: 15.81±1.67). Flecainide did not alter arrhythmia inducibility.

Conclusion: Naïve Plako+/-­‐ hearts do not demonstrate enhanced ventricular arrhythmia inducibility. Epicardial pacing has not yet revealed subtle conducKon defects within the murine ventricular myocardium. Young sedentary ARVC paKents are therefore likely to be at no greater risk of ventricular tachyarrhythmias than comparable people without the condiKon.

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