Identifying Best

Identifying Best Responders to Rx: Biomarkers & Protein Networks Peter Liu University of Ottawa Heart Institute University of Toronto HF Case Question•72 F with prevMI, on vacation quarantine, has progressive SOB, SOA, orthopnea, cough–No fever, no COVID testing–ER: pulmcongestion on CXR–BP 115/85, HF 89, chest crackles –RNA: LVEF 23%, LV volume increased•Started on Furosemide, ACEiand bB•Cr 120, K 4.5, NTproBNP4,500 HF Case Question•With so many evidence based HFrEFmedications, what is your preferred approach for this patient?Question:1.Use of ACEi/bB/Spiro good enough2.Must add Entresto±Ivabradine3.Consider also DAPA + Vericiguat4.Time to personalize HFrEFRx for Pt HF Therapy InequalityHFrEF•ACEi/ARB•B-Blockers•Mineralcorticoidantagonists•Ivabradine•Sacubitril/valsartan•SGLT2i (Dapa)•Vericiguat HFpEF•Mineralcorticoidantagonists•Sacubitril/valsartan Prospective Search of Rx Markers Perez-Garcia, Molero, et al., Cancer Treatment Reviews 2017; 53:79-97 ProteomicApplications in Heart Failure Gel -Free LC-MS Patient Samples from (Nested) Case ControlCohorts ± Aptamer DNA Arrays ±Machine Learning/AI ± ±Relevant Murine Models Ab ProxExtension Assay UrinePlasmaTissue(if available) Available Proteomic Technologies Network A(e.g. Immunity, Senescence) Network B(e.g. Metabolism)Network C(e.g. Matrix Remodeling) System BiolIntegration Responseto Rx RxTrial Biomarker ValidationPrecision MedicineBayes-Genis A, Liu P, Januzzi, et al, EurHrtJ 2020 Protein Clustering of HFrEF & HFpEF Statistically significant by 1-way ANOVA Control HFrEF HFpEF HF Biomarker Phenotypes Training Set (Biostat)N = 2516Validation Set (Scotland)N = 1738Tromp J, van der Meer P, et al., EurHeart J 2018; 39:4269-76 HF Biomarker Phenotypes Tromp J, van der Meer P, et al., EurHeart J 2018; 39:4269-76 HF Biomarker Phenotypes Tromp J, van der Meer P, et al., EurHeart J 2018; 39:4269-76 Ageing AgeingInflammatory Metabolic Inflammatory Growth/Hypertrophy Growth/Hypertrophy Who R Responders to CRT? 11 Cikes M, Bijnens B, et al, Eur J Heart Failure 2019; 21:74 - 85 Who R Responders to CRT? 12 Cikes M, Bijnens B, et al, Eur J Heart Failure 2019; 21:74 - 85 Models for Rx Outcomes OuwerkerkW, VoorsAA, et al., J Am CollCardiol2018; 71:386-98 Regular Med RxMax All Med Rx Biomarker Guided Event Free Survival HFrEFPrecision RxNO/Metab•Vericiguat(Cr, eGFR)•SGLT2i (Dapa)IGFBP7 (?) Heart Rate•B-Blockers•IvabradineRAASi•ACEi/ARB•Mineralo-corticoid antagonists•Sacubitril/valsartanNT-pro-BNP TOPCAT Spiro EffectBest in Low NTproBNPPts AnandI, Solomon S, et al., JACC Heart Failure 2017; 5:241-52 HF Response Biomarkers•Enable Precision Medicine Practice–Maximize benefit for responders–Minimize SE or waste for non-responders–Maximize cost-effectiveness of Rx•Provide insight into biology•Facilitate future therapeutic development The EndThank You