Heart failure with borderline left ventricular systolic dysfunction: what's new in prognosis and management? Adj Ass Prof Ong Hean Yee MBBCh BAO, ASCeXAM, FRCP, FESC Senior Consultant and Head of Department Department of Cardiology Khoo Teck Puat Hospital Disclosure Advisory Board Novartis, Boehringer Ingelheim, Bayer, Sanofi, Pfizer, Astra Zeneca Principle Investigator Novartis, Sanofi, Bayer, Astra Zeneca, Eli-Lilly, Amgen, Pfizer Sponsorship (2014-2015 only) Astra Zeneca, Bayer All Honorariums donated to Department Research and Training Fund Ejection Fraction not mentioned Diagnosis was based on Low • Cardiac Index High • PCWP (surrogate for LA / LVEDP) • Systemic Vascular Resistance Ejection Fraction not mentioned Diagnosis was based on Clinical Symptoms Oedema CXR Ejection Fraction < 45% used Ejection Fraction < 30 % vs < 50% NELSON, N COHN, GORLIN CIRC 1975, 52: 408 Heart Failure Preserved EF (HFPEF) Ziles N Engl J Med 2004;350:1953-9 Heart Failure Preserved EF (HFPEF) LVEDP ~ 5mmHg Ziles N Engl J Med 2004;350:1953-9 Heart Failure Preserved EF (HFPEF) LVEDP ~ 17mmHg LVEDP ~ 5mmHg Ziles N Engl J Med 2004;350:1953-9 Preserved versus Reduced Preserved EF Reduced EF TOPCAT (2014) N = 3445 Follow up 3.3 years Primary Endpoint: MACE NEJM 2014, 370: 1383-92 TOPCAT 2014 TOPCAT subgroup 2015 Russia / Georgia n = 1678 Younger Less AF / DM More MI / Hospitalisation Lower baseline creatinine CIRC 2015;131: 34-42 CIRC 2015;131: 34-42 CIRC 2015;131: 34-42 soluble Guanylate Cyclase - sGC Circulation 2011; 123: 2263-2273 Singapore Singapore, Singapore, 119228 Singapore, Singapore, 169609 Singapore, Singapore, 308433 Singapore, Singapore, 768828 JAMA 2015; 314(21): 2251-2262 SOCRATES JAMA 2015; 314(21): 2251-2262 SOCRATES Phase 2b Vericiguat (BAY1021189) JAMA 2015; 314(21): 2251-2262 SOCRATES Phase 2b JAMA 2015; 314(21): 2251-2262 Vericiguat https://clinicaltrials.gov/ct2/show/NCT02861534 LCZ-696 PARADIGM-HF NEJM 2014; 371: 993-1004 LCZ-696 https://clinicaltrials.gov/ct2/show/NCT01920711 HFREF HFPEF Aliskiren (DRI) ASTRONAUT JAMA 2013 Negative Serelaxin RELAX-AHF Lancet 2013 Mortality 37% lower Relax-AHF EHJ 2013 Negative LCZ-696 (ARNI) PARADIGM-HF NEJM 2014 Mortality 16% lower PARAGON-HF ongoing ??? Vericiguat (sGC) VICTORIA ??? VICTORIA ??? What’s New Diagnosis – stress testing Diagnosis – Biomarkers ST-2 / GDF-15 Treatment – ARNi / SCG agonist