Gershan Davis

Aggressive Cardiac Involvement in Systemic Lupus Erythematosus: A Case Report and a Comprehensive Literature Review

Background. We present the case of a 35-year-old gentleman who presented with an aggressive cardiomyopathy with normal coronary arteries. He was later diagnosed with systemic lupus-related cardiomyopathy. Methods. We undertook an extensive review of the literature regarding cardiac manifestations of lupus and used over 100 journals to identify the key points in pathology, diagnosis, and treatment. Results. We have shown that cardiac lupus can be rapidly progressive and, unless treated early, can have severe consequences. The predominant pathologies are immune complex and accelerated atherosclerosis drive. Treatment comprised of high-level immunosuppression.

Impact on service provision for non-invasive cardiac imaging following NICE recommendations: an observational study

Background Chest pain or discomfort due to angina can have a potentially poor prognosis, emphasising the importance of prompt and accurate diagnosis. The National Institute for Health and Clinical Excellence (NICE) published ‘Chest pain of recent onset’ guidelines in March 2010. These guidelines appraise the role of newer non-invasive modalities in cardiac imaging in the prompt and cost-effective diagnosis of coronary artery disease. Objective To study the service requirement for non-invasive cardiac imaging in patients with stable chest pain using current NICE guidance. Design Single-centre, 6-month (January 2010 to June 2010) observational study. Setting Rapid access chest pain clinics in a large university teaching hospital providing secondary care cardiology services. Methods Clinic letters were used to ascertain the type of chest pain and cardiovascular risk factors. The resting 12-lead ECG was examined for any ischaemic changes. Patients were then retrospectively allocated to an assessment pathway based on NICE guidance for the evaluation of stable chest pain. Pretest likelihood of coronary artery disease was calculated using Pryor et als table as published by NICE. Depending on the calculated pretest probability, their NICE-suggested investigation was determined. This included no further investigations, cardiac CT, functional imaging or invasive angiography. Results 500 patients were seen in rapid access chest pain clinics, 65 of which did not meet the referral criteria of having chest pain. On the basis of previous practice, 52% of patients were likely to have an exercise tolerance test. According to current NICE guidance as applied to our cohort of patients, 128 (30%) would have required functional imaging, 119 (27%) no further investigation, 95 (22%) cardiac CT, and 93 (21%) invasive angiography. Conclusion Functional imaging and then cardiac CT are the main investigations required in the assessment of patients with stable chest pain.

Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis

Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca2+ transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+ transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.

Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction

What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non‐diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes.

Use of the Joint British Society cardiovascular risk calculator before initiating statins for primary prevention in hospital medicine: experience from a large university teaching hospital

Introduction: Statin therapy is a well established treatment for hyperlipidemia. However, little is known about prescribing of statins for primary prevention in the real world, and even less about what happens to patients requiring primary prevention who are seen in a secondary care setting. The purpose of this research was to investigate the appropriateness of statin prescriptions by using the Joint British Society cardiovascular disease (JBS CVD) risk score for primary prevention in a large secondary care center. Methods: We retrospectively analyzed 500 consecutive patients in whom a statin prescription was initiated over a four-month period. We excluded patients who met secondary prevention criteria. We used the JBS CVD risk prediction chart to calculate 10-year composite risk. We also studied which statins were prescribed and their starting doses. Results: Of 500 patients consecutively started on statins in secondary care, 51 patients (10.2%) were treated for primary prevention. Of these, seven (14%) patients had a 10-year composite cardiovascular event risk of more than 20% (high-risk category), and were hence receiving appropriate therapy. Three main statins were prescribed for primary prevention, ie, atorvastatin (22 patients, 43%), simvastatin (25 patients, 49%), and pravastatin (four patients, 8%). The statins prescribed were initiated mainly at the 40 mg dose. Conclusions: Statin prescribing in secondary care for primary prevention is limited to about 10% of initiations. There is some overprescribing, because 86% of these patients did not require statins when risk-stratified appropriately. The majority of the prescriptions were for simvastatin 40 mg and atorvastatin 40 mg.

232 DIFFERENTIAL GENETIC EXPRESSION AND REDUCED LONGITUDINAL FUNCTION IN PATIENTS WITH DIABETES AND SEVERE AORTIC STENSOIS WITH A NORMAL EJECTION FRACTION

Introduction Aortic stenosis and type 2 diabetes mellitus are common conditions and patients with cardiovascular disease and type 2 diabetes tend to have a worse outlook than those with cardiovascular disease alone. We compared patients with severe aortic stenosis and diabetes to patients with severe aortic stenosis but no diabetes. We compared left ventricular (LV) function and expression of key genes in the left ventricle. Methods Two groups of patients with severe aortic stenosis (AVA of 1.0 cm2or less and LV ejection fraction >55%) and with (n=6) or without (n=8) type 2 diabetes were referred for aortic valve replacement. Patients had a full echocardiogram with speckle tracking prior to their operation and had a single apical LV needle biopsy taken just prior to the initiation of cardio-pulmonary bypass. The biopsies were flash frozen for mRNA expression. Expression of 48 mRNAs (responsible for ion channels and involved in energy metabolism and contractile performance in the heart) was measured by qPCR. Expression was normalised to 18S and differences were assessed using Student’s t-test (*P<0.05). Results Mean patient characteristics (with standard deviations) in both groups are shown below: Table 1   Group Age (years) Waist (cm) Weight (kg) BMI (Kg/m2) HbA1c (%) Control 78.8 (8.3) 35.8 (2.7) 79.4 (11.47) 27.8 (2.3) Diabetes 74.9 (12.8) 39.7 (8.8) 84.8 ( 21.4) 31.3 (6.9) 6.9 Mean echocardiogram parameters (with standard deviations) for the two groups are shown below: Table 2   Group LV Septal width (cm) LV End-Diastolic Volume (ml) LV Ejection Fraction (%) LV Longitudinal strain (%) MAPSE(cm) Control 1.6 (0.23) 76.2 (26.5) 63.9 (6.5) 18.3 (3.7) 1.6 (0.23) Diabetes 1.7 (0.48) 89.6 (15.6) 58.2 (2.6) 12.7 (2.5)* 1.1 (0.20)* Of the 48 genetic targets tested on the tissue samples we found an increase in patients with diabetes: NFKB-a proinflammatory transcription factor KIR 2.1 and KIR 3.1- potassium channels NCX 1-sodium-calcium exchanger ANKRD1- a transcription factor We found a decrease in patients with diabetes in: HERG- a potassium channel MTATP 6- a mitochondrial energy production gene NAV 1.5- a sodium channel Discussion We have shown a significant reduction in longitudinal left ventricular function (as evidenced by reduced MAPSE and longitudinal strain) in patients with diabetes mellitus and severe aortic stenosis compared to non diabetic controls. There was no difference in weight, BMI, waist circumference, normal ejection fraction, LV septal thickness and LV end diastolic volume. The left ventricular changes are accompanied by differential expression in several cardiac genes in patients with diabetes and may represent a subclinical cardiomyopathy that could be targeted for primary prevention of symptomatic cardiac disease.