* Shared first co-authors Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Stress-induced alteration of left ventricular eccentricity: an additional marker of multivessel CAD Alessia Gimelli, MD*1, Riccardo Liga, MD*2, Assuero Giorgetti, MD1, Mirta Casagranda, RT1, Paolo Marzullo, MD1, 3 1Fondazione Toscana G. Monasterio, Pisa; 2Cardio-Thoracic and Vascular department, University Hospital of Pisa; 3CNR, Institute of Clinical Physiology, Pisa * Shared first co-authors Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology BACKGROUND 1- In patients with multivessel coronary artery disease (CAD), the accuracy of myocardial perfusion imaging (MPI) can be diminished 2- Apart from perfusion and functional data, MPI on SPECT may also give information on LV three-dimensional structure, by the quantification of the LV eccentricity index (EI) 3- A lower EI, representing a more spherical left ventricle (LV), has been associated with the presence of CAD, ultimately predicting adverse patients prognosis 4- The possible clinical impact of abnormal values of LV EI in patients with preserved LV systolic function has not been yet evaluated Copyright American Society of Nuclear Cardiology

METHODS Study type: Retrospective Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology METHODS Study type: Retrospective Study subjects: 343 consecutive patients with chest pain and normal LV systolic function [ejection fraction (EF) >50%] that underwent MPI followed by coronary angiography within 3 months Study endpoints: Primary end point: the possible clinical value of the assessment of LV EI in patients with preserved LV systolic function submitted to MPI, and its ability in unmasking the presence of multivessel CAD Secondary end point: the interaction between stress-protocol (exercise vs vasodilator) and stress-induced LV functional impairment Study variables: eccentricity index; ejection fraction; multivessel CAD; summed difference score Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology RESULTS 50 55 60 65 70 No CAD Single-vessel CAD Multivessel CAD LV Ejection Fraction after Stress (%) Exercise stress-test LV Eccentricity Index after Stress Vasodilator stress-test A B ,75 ,8 ,85 ,9 ,95 P = 0.005 P < 0.001 P < 0.026 P = 0.461 P = 0.152 Relationships between CAD burden and (A) functional (EF) and (B) structural (EI) signs of stress-induced LV impairment on either exercise (left) or vasodilator (right) stress-test. Copyright American Society of Nuclear Cardiology

Suppl. Table 1 Predictors of Multivessel CAD in patients submitted to exercise-stress CZT Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology RESULTS Predictors of Multivessel CAD in patients submitted to exercise-stress CZT Variables Univariate OR (95% CI) P Multivariate OR (95% CI) Clinical data Age, years 1.02 (0.99-1.05) 0.158 NA Male sex, 1-0 1.06 (0.55-2.04) 0.874 Diabetes mellitus, 1-0 2.59 (1.42-4.71) 0.002 2.08 (1.17-3.71) 0.013 Hypercholesterolemia, 1-0 1.54 (0.87-2.75) 0.140 Hypertension, 1-0 1.53 (0.84-2.78) 0.162 Smoking, 1-0 1.72 (0.71-4.16) 0.226 LV structure and function at rest Stress end-diastolic volume, % 1.01 (0.99-1.02) 0.370 Stress ejection fraction, % 0.99 (0.95-1.02) 0.425 Eccentricity index (per 0.01 increase) 0.91 (0.84-0.98) 0.012 NS LV structure and function after stress 1.01 (1.00-1.02) 0.098 0.97 (0.94-0.99) 0.019 0.89 (0.83-0.96) 0.93 (0.88-0.99) 0.039 Perfusion data Mild ischemia (3<SDS≤7) 4.82 (2.03-11.44) <0.001 4.87 (2.04-11.63) Significant ischemia (SDS>7) 15.71 (6.62-37.30) 12.92 (5.37-31.08) Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology CONCLUSIONS 1- In patients with preserved LV systolic function, the presence of multivessel CAD associates with significantly more impaired values of post-stress LV eccentricity as a measure of stress-induced transient LV remodeling 2- Interestingly, alterations of post-stress LV EI were limited to patients undergoing exercise stress-test, while disappeared in those submitted to vasodilator stress 3- Only a marginal fraction of the variability of post-stress LV EI could be explained by alterations of either EF or end-diastolic volume, confirming the possible value of this novel parameter of adverse remodelling Copyright American Society of Nuclear Cardiology