State of the Art: acute heart failure Is it just congestion?

Transcription

1 ESC CONGRESS 2017 Barcelona, August 2017 State of the Art: acute heart failure Is it just congestion? S.B. Felix, FESC Klinik für Innere Medizin B Ernst-Moritz-Arndt-Universität Greifswald

2 ESC CONGRESS 2017 Barcelona, August 2017 SB Felix Dept. of Internal Medicine B University Medicine Greifswald Acute heart failure Is it just congestion? Declaration of Interest Lectures fees: Novartis, Bayer, Berlin Chemie, Servier, Cardiorentis; Actelion Research Grants: Bayer, Novartis

3 Acute Heart Failure Definition Symptoms Prognosis Prognostic factors - clinical parameters - biomarkers Cardio-pulmonary-renal interactions (CPRI) Therapy

4 Acute failure of the left ventricle Acute de novo heart failure (e.g. acute myocardial infarction, myocarditis, ) Acutely decompensated heart failure (ADHF) Transition from chronic heart failure to acutely decompensated heart failure Worsening HF De novo HF End-stage HF Gheorghiade et al. J Am Coll Cardiol 2013;61: Ponikowski et al. Eur Heart J. 2016;37:

5 Acute Heart Failure Definition Symptoms Precipitating factors Prognosis Prognostic factors - clinical parameters - biomarkers Cardio-pulmonary-renal interactions (CPRI) Therapy

6 AHF symptoms ADHERE cumulative enrollment (October 2001 through December 2003) ADHERE 120,000 Discharges clean as of current transfer 90 Total discharges ,000 Patients (%) Patient hospitalizations 100, ,000 40, , / / / / / / / / / / / / / / / /0 9 0 Date ea o n sp Dy a es l Ra l ra m de oe he ip er P AHF=acute heart failure Adams et al. Am Heart J 2005;149:

7 Acute Heart Failure Definition Symptoms Prognosis Prognostic factors - clinical parameters - biomarkers Cardio-pulmonary-renal interactions (CPRI) Therapy

8 EuroHeart Failure Survey II (2,981 AHF patients) 1-year mortality 3-month mortality In-hospital mortality Mortality (%) Total Survey ADCHF De novo HF Harjola et al. Eur J Heart Fail 2010;12:

9 Acute Heart Failure Definition Symptoms Prognosis Prognostic factors - clinical parameters - biomarkers Cardio-pulmonary-renal interactions (CPRI) Therapy

10 Improvement in dyspnea is associated with a reduction in both PCWP and PAPmean Solomonica et al. Circ Heart Fail. 2013;6:53-60 PROTECT study: multivariate analysis of the association between dyspnoea relief and mortality Variable HR 95% CI p value Dyspnoea relief at Days 2 and , 0.62 < Age, per 1 year increase , NYHA class before admission IV vs. I/II/III , Systolic blood pressure at screening, per 1 mmhg increase , Screening BNP >750 or NT-proBNP >3,000 pg/ml , Day 1 serum sodium; per 1 meq/l increase , 0.95 <0.001 Baseline creatinine clearance, per 1 ml/min increase , day mortality Metra et al. Eur Heart J 2011;32:

11 Biomarkers of congestion Mortality rates for patients admitted for acute decompensated heart failure discharged with different absolute and relative NT-proBNP levels Six-month all-cause mortality rates Stienen et al. Eur J Heart Failure 2015; 17:

12 Risk for death and markers of impaired organ function/damage Mechanism of cardiac troponin release in heart failure Increased wall stress Epicardial CAD Reversible injury Myocyte necrosis Cardiac troponin release Oxidative stress Myocyte apoptosis Altered calcium handling Neurohormonal activation Troponin degradation products Inflammatory cytokines Kociol et al. J Am Coll Cardiol 2010;56:

13 RELAX-AHF Risk for death by early changes in markers of impaired organ function/damage Metra et al. J Am Coll Cardiol 2013;61:

14 Acute Heart Failure Definition Symptoms Prognosis Prognostic factors - clinical parameters - biomarkers Cardio-pulmonary-renal interactions (CPRI) Therapy

15 Consequences of acute (decompensated) LV failure cardio-pulmonary-renal interactions (CPRI) Congestion LV RV Hypoperfusion LV

16 Stangl et al. Circulation 2000;102:

17 CPRI in Heart Failure LV function deterioration! Congestion is an important component of organ damage in AHF Deterioration of renal function Modified from Guazzi et al. Int J Cardiol 2013; 169:

18 Cardiorenal syndrome Definition Executive Summary from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) McCullough et al. Blood Purif. 2014;37 Suppl 2:2-13

19 The cardiorenal syndrome Chronic cardiorenal syndrome (type 2) Acute cardiorenal syndrome (type 1) Roubille et al. Blood Purif 2014;37(suppl 2):20 33

20 ADHF organ damage is not limited to the heart Cardiorenal syndrome type 1: acute kidney injury and dysfunction in the patient with acute cardiac illness, most commonly ADHF Reduced renal autoregulation Increased susceptibility Vasoconstriction Relative decrease in cardiac output Arterial underfilling Sympathetic nervous system RAAS Arginine vasopressin Endothelin Decreased perfusion pressure ADHF Ineffective natriuretic peptides Kinin-kallikrein system Prostaglandins Endothelial relaxin factor Increased preload Venous congestion Functional (pre-renal) Glomerularinterstitial damage AKI Sclerosis fibrosis Increased venous pressure Repeated episodes of AKI Uremic milieu Parenchymal damage CKD Ronco et al. J Am Coll Cardiol 2012;60:

21 Importance of Venous Congestion for Worsening of Renal Function in Advanced Decompensated Heart Failure Worsening renal function (increase of serum creatinine 0.3 mg/dl during hospitalization) Mullens et al. J Am Coll Cardiol 2009;53:589 96

22 Gut congestion Mann DL Heart Fail Rev 2001;6:71-80 Anker et al. Am J Cardiol 1997;79: Bahls M & Felix SB Eur Heart J 2016;7:

23 Acute Heart Failure Definition Symptoms Precipitating factors Prognosis Prognostic factors - clinical parameters - biomarkers Cardio-pulmonary-renal interactions (CPRI) Therapy

24 ESC guidelines 2016 Ponikowski et al. 2016;37:

25 ESC guidelines 2016 Decongestion in acute heart failure Ponikowski et al. 2016;37:

26 Dose Diuretic Strategies in Patients with Acute Decompensated Heart Failure 308 patients with ADHF: treatment with i.v. furosemide Bolus every 12 h * High dose Low dose Continuous infusion High dose Low dose * High dose: 2.5 times the previous oral dose Low dose: equivalent to the patient s previous oral dose Coprimary end points - patients global assessment of symptoms, quantified as the area under the curve of the score on a visual-analogue scale over the course of 72 h - change in the serum creatinine level from baseline to 72 hours

27 Dose Felker et al. N Engl J Med 2011;364:

28 Dose dose increase at 48 h switch to oral diuretics at 48 h 30 % patients * * high dose low dose 5 0 From Felker et al. N Engl J Med 2011;364:

29 Loop Diuretic Efficiency Prognostic Importance in Acute Decompensated Heart Failure Study populations - n=675 consecutive admissions with a primary discharge diagnosis of HF (Univ. Pennsylv.) - n=390 patients in ESCAPE dataset Diuretic efficiency = net fluid output produced per 40 mg furosemid equivalents low dose high efficiency high high dose dose high efficiency low dose low efficiency high dose low efficiency - High Efficiency = DE > median - Low Efficiency = DE < median Low or high loop dose: > or < the median value, which was 280 mg in the Penn cohort and 240 mg in 24 h in the ESCAPE cohort. Testani, J. M. et al. Circ Heart Fail. 2014;7:

30 Diuretic treatment in AHF Worsening renal function (WRF; e.g. increase of serum creatinine during ) in ADHF is a common condition (in clinical studies: SAE). Is worsening of renal function during treatment with diuretics of prognostic relevance?

31 WRF alone is not an independent determinant of outcomes in patients with AHF but has an additive prognostic value when it occurs in patients with persistent signs of congestion 1-year death or urgent heart transplantation No WRF/No Congestion WRF/No Congestion No WRF/Congestion WRF/Congestion Metra et al. Circ Heart Fail 2012;5;54-62

32 ADHF prediction of all-cause and cardiovascular mortality Inhospital-WRF All-cause Death 1y-WRF All-cause Death Ueda et al. J Am Heart Ass 2014;3:1-6

33 ESCAPE Potential Effects of Aggressive Decongestion During the Treatment of Decompensated Heart Failure on Renal Function and Survival Hemoconcentration was associated with a substantially lower risk of mortality. Aggressive decongestion, even in the setting of worsened renal outcomes, may have a positive impact on survival? Testani et al. Circulation 2010;122;

34 Vitious Circle in Acute Decompensated Heart Failure Cardiac Lesion Depressed Ventricular Performance SVR Hypervolemia Cardiac Output Therapeutic target Therapeutic target Decrease of afterload useful in hypertensive AHF Decrease of preload Neurohumoral Activation Sympathetic Nervous System RAAS Endothelin

35 ESC guidelines 2016 Vasodilators in acute heart failure Intravenous vasodilators have dual benefit by decreasing venous tone (to optimize preload) and arterial tone (decrease afterload). Consequently, they may also increase stroke volume. Vasodilators are especially useful in patients with hypertensive AHF, whereas in those with SBP < 90 mmhg (or with symptomatic hypotension) they should be avoided. Intravenous vasodilators: second most often used agents in AHF for symptomatic relief; however, there is no robust evidence confirming their beneficial effects. Ponikowski et al. 2016;37:

36 Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema Inclusion criteria Patients with pulmonary edema (chest X-ray), oxygen saturation < 90% Initial treatment Oxygen 10 L/min, furosemide 40 mg i.v., morphine 3 mg i.v. 110 patients randomized Group A * 56 patients Group B * 54 patients * 3 mg ISDN i.v. every 5 min * 80 mg bolus of furosemide i.v. every 15 min and 52 patients completed trial 52 patients completed trial ISDN 1 mg/h, increased by 1 mg/h every 10 min Treatment was continued in both groups until oxygen saturation increased to at least 96% or mean arterial blood pressure decreased by at least 30% or to lower than 90 mm Hg Cotter et al. Lancet 1998; 351:

37 Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema High dose ISDN High dose Furosemide + low dose ISDN Cotter et al. Lancet 1998; 351:

38 ESC guidelines 2016 Hypoperfusion Inotropic agents in acute heart failure Ponikowski et al. 2016;37:

39 Acute Heart Failure Definition Symptoms Prognosis Prognostic factors - clinical parameters, in-hospital worsening HF - biomarkers and end-organ damage Therapy: Novel drugs

40 Clinical Trials in worsening HF/ADHF Trial Agent Outcome Pts Effects on Symptoms 951 Effects on OPTIME-CHF Milrinone AEs VERITAS Tezosentan EVEREST Tolvaptan No Yes PROTECT Rolofylline No No Survive Levosimendan vs. Dobutamine No No VMAC Nesiritide Yes ASCEND-HF Nesiritide No No RELAX-AHF-2 Serelaxin No No TRUE-AHF Urodilatin No No No No No

41 Requiescat in pacem Milrinone Tolvaptan Tezosentan Rolofylline Cinaciguat Nesiritide Serelaxin Urodilatin

42 Summary ADHF Poor prognosis (1-year mortality: 25 30%) Congestion is a key component and an important prognostic factor No evidence confirming beneficial prognostic benefit of any drug treatment What is the right endpoint of AHF studies? - mortality? - improvement of symptoms (e.g. congestion)? - worsening of heart failure?