Heart failure: what should be changed? Prof. Gerasimos Filippatos Attikon University Hospital

Disclosures Chair or Committee Member of trials or registries sponsored by Novartis, Bayer, Cardiorentis, Servier Research Grants: European Union Associate Editor: European Heart Journal, Int J Cardiol Journal of CV Medicine

EVERYTHING

Outcome in acute HF is still poor DOSE CARRESS-HF Death, Rehospitalization or ER visit 40% at 60 days

Chronic HF survival rates have improved over time with the advent of new therapies Temporal trends in 5-year mortality after the diagnosis of HF by gender show improvements in survival Survival (%) 100 80 60 40 Men Survival (%) 100 80 60 40 Women 1996 2000 1991 1995 1985 1990 1979 1984 20 20 0 0 1 2 3 4 5 6 7 8 9 10 Years 0 0 1 2 3 4 5 6 7 8 9 10 Years... nevertheless, the 5-year mortality rate remains high Population-based cohort study analysing data from the Rochester Epidemiology Project, Minnesota, USA. 4,537 patients with a diagnosis of HF between 1979 and 2000 were included. Framingham criteria and clinical criteria were used to validate the diagnosis. Roger et al. JAMA 2004;292:344 50

WE NEED Better Diagnosis Better Classification Study the Epidemiology around the world Understand better the pathophysiology Therapies that improve mortality and morbidity Is treatment of Acute HFPEF different from Acute HFREF?

Better Diagnosis Better Classification Study the Epidemiology around the world Understand better the pathophysiology Therapies that improve mortality and morbidity Is treatment of Acute HFPEF different from Acute HFREF?

www.escardio.org/guidelines Diagnostic algorithm for a diagnosis of heart failure of non-acute onset

Diagnostic algorithm for a diagnosis of heart failure of non-acute onset www.escardio.org/guidelines

Causes of elevation of natriuretic peptides levels Interpretation of Natriuretic Peptides

13 New Classification and Diagnosis New Classification! Heart failure with preserved, mid-range and reduced EF it is only in patients with HFrEF that therapies have been shown to reduce both morbidity and mortality

14 Signs (± symptoms) of HF Structural abnormalities LAVI >34ml/m 2 + HFpEF: EF 50% HFmrEF: EF 40-49% + Functional abnormalitie s E/e avg 13 Diagnosis of HFpEF/ HFmrEF Limited data (Unmet Need!) Cut-offs arbitrary More criteria; greater certainty of diagnosis Diastolic stress test? Invasive hemodynamic measurements? LVMI >115g/m 2 (m) >95 g/m 2 ( f ) e average (lateralseptal) < 9 cm/s www.escardio.org/guidelines

Heart Failure: TNM-Like Classification HLM ClassificationIn each column, different stages of heart (H-1 to H-4), lung (L-0 to L-3), and peripheral organ involvement (i.e., kidney, liver, and brain [M-0 to M-3] Francesco Fedele, Paolo Severino, Simone Calcagno, Massimo Mancone Journal of the American College of Cardiology, Volume 63, Issue 19, 2014, 1959 1960

from Filippatos et al Heart Fail Rev 2007 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

Classification of AHFS ACS with Heart Failure PULMONARY EDEMA Hypertensive AHF or Vascular AHF or De Novo AHF Right Heart Failure Normotensive AHF or Cardiac Failure or Acutely Decompensated Chronic HF Hypotensive AHF/ Cardiogenic shock Filippatos G et al. Heart Failure Rev 2007

Management of patients with acute heart failure based on clinical profile during an early phase www.escardio.org

Gheorghiade and Braunwald. JAMA 2011;305:1702-3.

EVEREST Trials: Continental Differences 4133 patients admitted with AHF and reduced LVEF on standard medical therapy followed 9.9 months North America South America Western Europe Eastern Europe P-value 1-year Estimate, %, (95% CI) Death 30.4 (27.6-33.1) 27.2 (23.3-30.8) 27.1 (23.0-31.1) 20.5 (18.1-22.8) <0.0001 CV death/hf hospitalization 52.5 (49.4 55.3) 41.6 (37.3 45.6) 47.3 (42.6 51.7) 35.3 (32.4 38.0) <0.0001

Variation in death and re-admission =30 days =1 year 40 Death 60 HF re-admission Proportion (%) 30 20 10 45 30 15 0 Scotland Glasgow Alberta Turin Denmark 0 land gow erta urin ark

REPORT-HF Registry: Global Outreach # Modified from Filippatos et al. Eur J Heart Fail. 2015;17(5):527-33;

AHF: Pathophysiology Myocardial injury Apoptosis Extracellular matrix Acute BP Arrhythmias Ischemia Age, LVH Renal dysfunction Impaired relaxation, Stiffness Neurohormonal activation Increased Afterload Filling pressures Stroke volume Filippatos G et al. Am J Physiol 1999;277:H445, Jain P et al. Am Heart J. 2003;

Potential pathogenetic pathways linking heart failure with renal dysfunction. Filippatos G et al. Eur Heart J 2014

From: Braunwald s Heart Disease. 9th ed. Philadelphia,

AHF (and WRF) in patients with or wo CKD

What to do next? 1. Increase furosemide dose 2. Ιntravenous infusion rather than bolus therapy 3. Substitution of an ineffective loop diuretic for another one 4. Add metolazone and/ or potasium sparing diuretic 5. Add dopamine at 2-5 mcg/k/m 6. Withdraw b-blocker and/ or ACE inhibitor 7. Add dobutamine 8. Add levosimendan 9. Start ultrafiltration 10. Start dialysis 11. Insert IABP 12. Insert another device Maisel A, Filippatos G. In: Heart Failure. Publisher Jaypoor, 2014

EURObservational Research Programme Acute HF: persisting congestion at discharge and all-cause mortality during the follow-up 81,6% 24,1% Pulmonary and/or Peripheral congestion At admission 11,3% p<.0001 No 20,8% At discharge Yes

Early drop in systolic blood pressure and worsening renal function in AHF: renal results of Pre-RELAX-AHF European Journal of Heart Failure vol 13, pages 961-967, 2014 DOI: 10.1093/eurjhf/hfr060

Impact of Venous Congestion on Glomerular Net Filtration Pressure Jessup, M. et al. J Am Coll Cardiol 2009;53:597-599

Treatment Algorithm Available online on Eur J Heart Fail We are HFA www.escardio.org

OPTIMIZE-HF: distribution of patients LVEF Fonarow et al. J Am Coll Cardiol. 2007; 50(8):768

AHF with preserved vs reduced EF: effect of new therapies The two larger RCT trials of ultrafiltration in AHF (UNLOAD and CARRESS-HF) included AHF patients with HFpEF but did not find any significant differences in response to ultrafiltration in HFpEF versus HFrEF. Bart et al. N Engl J Med. 2012; 367(24):2296 2304. In ASCEND trial, nesiritide marginally improved symptom relief without effect on renal function or clinical outcomes, and there was no differential response according to EF (< or 40 %). O'Connor CM et al. N Engl J Med. 2011; 365(1):32 43 In RELAX-AHF, 45 % of patients had EF >40 %, while serelaxin improved dyspnea scores both in patients with HFpEF and HFrEF. Filippatos et al Eur Heart J 2013

Forget Anything?

0 % Public don t know how to recognise HF Proportion of general public recognising symptoms of heart failure (combination of breathlessness, tiredness and swollen ankles) 5 0 5 0 NL France Spain Ital Romania UK Sweden Poland Germany

Public do recognise other cardiovascular conditions General public recognition of description of typical symptoms/signs of three common cardiovascular problems 50 38 % 25 13 0 heart 1 attack stroke 2 heart failure 3

MEMBERS: 56 National Cardiac Societies AFFILIATED MEMBERS: 26 National Cardiac Societies

29 April 2 May 2017 PARIS, France 4 days of scientific exchange 6 100+ healthcare professionals 2 000+ abstracts and cases submitted 110+ scientific sessions 300+ expert faculty members 100+ countries represented 45+ industry sessions/workshops Call for abstracts: November 3 January 13