Treating the patient with acute heart failure. What do we really know? Principles of acute heart failure treatment

Transcription

1 ESC Aug - 3Sep, 2012, Munich, Germany Treating the patient with acute heart failure. What do we really know? Principles of acute heart failure treatment Marco Metra, MD, FESC Cardiology University of Brescia, Italy Disclosures: Co-chairman of the RELAX-AHF trial, received honoraria from Abbott vascular, Bayer, Corthera, Novartis.

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3 tachycardia coronary perfusion pressure MVO 2 Pathophysiologic mechanisms in acute heart failure Myocardial ischemia LV afterload CO / LVEDP Cardiac dysfunction systolic diastolic End-organ hypoperfusion venous pressure Neurohormonal activation RAA SNS - ADH Inflammatory activation Diuretic use Diuretic resistance Renal changes / renal dysfunction Na-H 2 O retention Congestion Fluid redistribution to the lungs Lung congestion LV wall stress LV preload Metra, Brutsaert, Dei Cas, Gheorghiade. ESC Intensive Acute Cardiac Care textbook

4 Factors which influence clinical presentations & prognosis of AHF Fluid status Blood pressure (afterload mismatch, LV function?) Myocardial ischemia Kidney dysfunction Other pathogenic mechanisms Neurohormonal activation Endothelial dysfunction Inflammatory activation Time of treatment

5 Symptoms in patients with acute HF in major registries Study, year No of patients dyspne a, % Orthopn ea, % Pulm. Rales, % Peripheral edema, % Rudiger et al ADHERE, , IMPACT-HF, OPTIMIZE-HF, , Goldberg et al Tavazzi et al ALARM-HF, / 66* 55/ 72* 50/ 39* From 1 Rudiger et al., Eur J Heart Fail 2005;7:662-70; 2 Pang et al., Eur Heart J 2008; 29:816; 3 O Connor et al., J Card Fail 2005;11:200-5; 4 Gheorghiade et al., JAMA 2006;296: ; 5 Goldberg et al. Am J Med 2005;118:728-34; 6 Tavazzi et al. Eur Heart J 2006;27: ; 7 Parissis et al. Eur J Heart Fail 2010; 12, ; * ADHF/ APE

6 Changes in epad Systolic heart failure Diastolic heart failure Circulation 2008;118:

7 Number of patients Initial treatment in the patients hospitalized for HF: ADHERE registry Costanzo et al. Am Heart J 2007;154:267277

8 Association between patient-assessed dyspnoea status and body weight change at inpatient Day 1. Pang P S et al. Eur Heart J 2009;30:

9 Weight changes after HF hospitalization are predictive of subsequent re-hospitalization: results from EVEREST Blair, J. E.A. et al. Eur Heart J :

10 Weight changes after HF hospitalization are not predictive of mortality: results from EVEREST Blair, J. E.A. et al. Eur Heart J :

11 Freedom from congestion predicts good survival also in patients with advanced HF 146 pts with NYHA IV 4-6 weeks after discharge reevaluated for congestion Criteria: 1. Orthopnoea 2. JVP 3. Oedema 4. Weight gain 5. baseline diuretics year survival (%) 0 crit (n=80) 1-2 crit (n=40) High-risk group 3 crit (n=26) Orth+ (n=33) Lucas et al., Am Heart J 2000;140:840

12 Bedside Cardiovascular Examination in Patients With Severe Heart Failure Pulmonary rales Jugular vein distension Butman et al. J Am Coll Ccrdiol 1993,

13 Probability of an HFE for 261 patients during a 6- month period in relation to chronic daily epad Copyright 2010 American Heart Association Stevenson, L. W. et al. Circ Heart Fail 2010;3:

14 Wireless pulmonary artery haemodynamic monitoring improves outcomes in HF: CHAMPION trial Abraham et al. The Lancet. 2011; 377: 658

15 Fraction of patients Fraction of patients Prognostic value of NT-ProBNP at discharge in patients hospitalised for AHF 1 Cardiac mortality 1 Cardiac mortality or CV Hospitalizations Patients at risk NT-ProBNP: P< Discharge NT-ProBNP <6078 Discharge NT-ProBNP > Days Patients at risk NT-prBNP: P< Discharge NT-ProBNP <3275 Discharge NT-ProBNP >3275 < < > > Days Metra et al. Eur J Heart Fail. 2007;9:

16 Factors which might influence clinical presentations & prognosis of AHF Fluid overload Blood pressure (afterload mismatch?) Myocardial ischemia Kidney dysfunction Others Neurohormonal activation Endothelial dysfunction Inflammatory activation

17 Spectrum of AHFS pathophysiological mechanisms Main mechanism of onset Cardiac (central / systolic) contractility Sodium and water renal retention Vascular (peripheral / diastolic) afterload and/or predominant LV diastolic dysfunction Main cause of symptoms Fluid accumulation Fluid redistribution to the lungs Gain in body weight Yes No Onset Gradual (days) Rapid (hours) Main symptom Fatigue Dyspnoea Systolic BP Normal to low Normal to high LV filling pressure May be low with low CO High LVEF & Cardiac output Low Normal Metra, Brutsaert, Gheorghiade, Dei Cas,. ESC Intensive Acute Cardiac Care textbook

18 Spectrum of AHFS pathophysiological mechanisms Main mechanism of onset Cardiac (central / systolic) contractility Sodium and water renal retention Vascular (peripheral / diastolic) afterload and/or predominant LV diastolic dysfunction Main cause of symptoms Fluid accumulation Fluid redistribution to the lungs Gain in body weight Yes No Onset Gradual (days) Rapid (hours) Main symptom Fatigue Dyspnoea Systolic BP Normal to low Normal to high LV filling pressure May be low with low CO High LVEF & Cardiac output Low Normal Metra, Brutsaert, Gheorghiade, Dei Cas,. ESC Intensive Acute Cardiac Care textbook

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20 mmhg / ml 44 patients: Echo during AHPE and >48 hours afterwards; 20 asymptomatic HBP patients (control); data as mean±se 4 Arterial impedance p= ,0 Arterial impedance / ventricular impedance ratio p= ,5 1,0 0,5 0 AHPE F-Up Controls 0,0 AHPE F-Up Controls AHPE F-Up Controls AHPE F-Up Controls Am J Cardiol 2012; 109: 1472

21 From: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes Gheorghiade & Braunwald. JAMA. 2011;305(16): doi: /jama Date of download: 8/27/2012 Copyright 2012 American Medical Association. All rights reserved.

22 Initial assessment of patient with suspected acute heart failure Authors/Task Force Members et al. Eur Heart J 2012;33:

23 Predicted value of VAS AUC change Increased symptom-improvement with the novel vasodilator, relaxin, in AHF patients with elevated BP. Results from Pre-Relax-AHF Placebo Relaxin 30 mcg/kg/m Systolic blood pressure, mmhg Teerlink et al. Eur Heart J 2009 ; 30 ( Abstract Supplement ), 164

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25 % of patients LVEF units Cause of AHF According to SBP: OPTIMIZE-HF Study patients FROM 259 us HOSPITALS LV Systolic dysfunction < >161 SBP quartiles, mmhg LV Ejection fraction < > SBP quartiles, mmhg Gheorghiade et al., JAMA 2006; 296:2217

26 Cause of AHF According to SBP: OPTIMIZE-HF Study patients FROM 259 us HOSPITALS % of patients In-hospital mortality < >161 SBP quartiles, mmhg % of patients Postdischarge mortality < >161 SBP quartiles, mmhg Gheorghiade et al., JAMA 2006; 296:2217

27 Limitations of Inotropic Agents Tachyarrhythmias ventricular arrhythmias ventricular rate in atrial fibrillation Myocardial ischemia progression of LV dysfunction? Hypotension / coronary hypoperfusion myocardial VO 2 (contractility & HR) Mechanisms cytoplasmic Ca 2+ Myocardial efficiency (work/vo 2 )? Vasodilation /hypotension

28 Effects of inotropic stimulation on the relationship between subendocardial blood flow and infarct size in anesthetized, open-chest pigs Schulz, Rose, Martin, Brodde, Heusch. Circulation 1993; 88:

29 Mean Change From Baseline, mm hg SURVIVE: Mean Change From Baseline in Hemodynamic Parameters Through 5 Days by Treatment Group Systolic Blood Pressure Dobutamine Levosimendan Study Assessment, hours Mebazaa, Nieminen, Packer et al. JAMA 2007;297:

30 Factors which might influence clinical presentations & prognosis of AHF Fluid overload Blood pressure Myocardial ischemia Kidney dysfunction Others Neurohormonal activation Endothelial dysfunction Inflammatory activation

31 AHF & myocardial ischaemia Acute coronary syndromes Myocardial infarction/unstable angina with large extent of ischemia and ischemic dysfunction Mechanical complication of acute myocardial infarction Right ventricular infarction Chronic coronary artery disease Ischaemia / necrosis precipitated by AHF Non-ischaemic cardiomyopathy Ischaemia / necrosis precipitated by AHF?

32 Prevalence of Detectable (>0.01 pg/ml) Troponin T in patients hospitalized for HF 46% Coronary artery disease 26% Idiopathic dilated cardiomyopathy 26% 28% 60% 14% TnT (1 sample) TnT (>1 sample) No TnT TnT (1 sample) TnT (>1 sample) No TnT Metra et al., Eur J Heart Fail. 2007;9:776-86

33 Prognostic role of Troponin release in patients hospitalized for acute heart failure Metra et al. Clin Res Cardiol Aug;101(8):663-72

34 Factors which might influence clinical presentations & prognosis of AHF Fluid overload Blood pressure Myocardial ischemia Kidney dysfunction Others Neurohormonal activation Endothelial dysfunction Inflammatory activation

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36 Cardio-renal interactions in heart failure and kidney disease Metra M et al. Eur Heart J 2012;eurheartj.ehs205

37 Kidney dysfunction in heart failure Metra, Cotter, Gheorghiade, Dei Cas, Voors. Eur Heart J published online August 10, 2012

38 Death or urgent treatment in patients subdivided on the basis of volume status and WRF No WRF / No Congestion WRF / No Congestion No WRF / Congestion WRF & Congestion WRF = worsening renal function Metra et al. Circ Heart Fail 2012 Jan 1;5(1):54-62.

39 Effect of an increase in cystatin C on mortality in patients with a small rise in creatinine during HF hospitalization No change in s-creatinine creatinine>0.2 mg/dl, No change cystatin C creatinine>0.2 mg/dl, cystatin C>0.3 mg/l Lassus J P et al. Eur Heart J 2010;31:

40 Multimarker Testing with ST2 and BNP and Rates of Death After Acute Heart Failure Rehman et al. J Am Coll Cardiol 2008;52:

41 % of patients % of patients One-year outcomes in patients with HF: Italian IN-HF Registry (n=5610) 50 Mortality 50 Hospitalizations , ,1 3,8 Chronic HF 4,7 14,5 New onset HF 7,8 19,9 Worsening HF ,5 5,8 17,2 16,3 Chronic HF New onset HF 29,5 Worsening HF Cardiovascular Non CV Cardiovascular Non CV Courtesy of L. Tavazzi and A. Maggioni

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43 Comprehensive assessment and cardiac reconstruction Pang P S et al. Eur Heart J 2010;31: