1. MRI Detection of Sub Clinical Structural Cardiac Dysfunction in HIV Positive Men Dr Aisling Loy

2. Murray et al, Lancet 2010 BACKGROUND Cardiovascular Disease in context 2

3. Evidence linking HIV and CVD Faceboo k 200,000 Clinical care options 2010 3 BACKGROUND

4. Inflammatory Effect Drugs Smoking Insulin Resistance Genetic s Family History Platlet Activation Causes of CVD in HIV 4 Dyslipidaemia Immune Dysfunction Coagulation Endothelial Dysfunction Hypertension v BACKGROUND

5. BACKGROUND Cardiac MRI We are one of the first groups world wide to utilise cardiac MRI in the study of HIV positive patients 5 Used to detect multiple forms of cardiac pathology, even in absence of symptoms. Gives us better understanding of early pathology process. IV Gadolinium used to detect damaged myocytes

6. U se Cardiac MRI to characterise Cardiovascular Morphology and Function in a HIV positive male population on ART Compare to age matched HIV negative controls Interrogate the effects of ART, viral status and traditional cardiovascular risks Determine the prevalence of unrecognised myocardical infarction. OUR RESEARCH AIMS 6

7. Method 168 HIV + men on ART. Prospectivively recruited. Baseline demographics, cardiovascular risks, ECG, HIV parameters and ART Hx was recorded Cardiac function was determined using CMR with IV gadolinium Results were analysed using SPSS software 7 OUR RESEARCH

8. 38% FAM HX OF HEART DISEASE 47yrs Demographics 25.5 72% MSM 158 caucasian 10 Sub Saharan 8 MEDIAN AGE MEDIAN BMI 8.6YRS median time Since Diagnosis Range = 3mths- 26.5yrs Median CD4=600 All are virally Suppressed 26% on Statins 65% On NNRTI INFOGRAPHIC

9. RESULTS Data Table 9 PATIENT/CMR FINDINGS CASES (N=168) CONTROLS (N=34)P VALUE AGE(mean, yrs) 46.49(+/- 8.68)43(+/-8.5)*0.03 Smoking Pk Yrs 13.7(+/-17.7)5.58(+/-9.41) *<0.001 Framingham Risk 9.9(+/-7.48)9.6(+/-8) 0.64 Known HTN(%)16.711.80.648 BMI( Kg/m 2 )25.527.20.529 Anteroseptal Wall Thickness (mean, mm) 10.7 (+/-2) 9.8 (+/-1.93) *0.021 E/A ratio(mean)1.33(+/-0.46)1.44(+/-0.4)0.144 Presence of Late Gad enhancement (LGE) 700.21

10. RESULTS Significant Results 7 cases of clinically significant Late Gadolinium enhancement detected 8/168 diastolic wall thickness >14mm 10 Anteroseptal wall thickness significantly greater in Cases v Controls p=0.021

11. P Value <0.05 Analysis of factors contributing to AS wall thickness RESULTS Multivariate Regression Analysis 11 BMI0.01 Current NNRTI based regimen 0.019 Family Hx of CVD 0.046 Framingham risk0.035 Significant contributors

12. RESULTS Late Gadolinium Enhancement Not statistically significant but clinically significant All asymptomatic 4/7 consistent with prior myocarditis 12 3/7 consistent with prior MI

13. Conclusion 13 Structural changes linked to ART may contribute to early cardiac death. Hypothesis generating study. MRI not clinical tool, don’t advocate this. Pathophysiology of CVD in HIV still unclear

14. 14 Further assessment of what is causing increased AS wall thickness Potential confounders of diet and genetics Not sufficiently powered to dissect out specific ART links Large prospective study to ascertain direct HIV/ART effects Limitations

15. WHAT NEXT? Future plans Spectroscopy on remaining cases and controls to assess Triglyceride deposition Recently published data showed high burden of myocardial Fibrosis, 76% in HIV patients. 15 30 More case and 30 more controls With TI mapping to assess Cardiac fibrosis Further assessment of associations between ART, dyslipidaemia, HIV and structural cardiac dysfunction

16. Dr Caroline Daly Ms Siobhan O’Dea Professor Fiona Mulcahy Consultant Cardiologist Research Nurse Consultant GU/HIV Physician Dr Roisin Morgan Cardiology SPR ACKNOWLEDGEMENTS 16 Our Research Team Special thanks to AVEC for funding.