ESC Congress 2011 27-31 August. Paris, France. Acute heart failure syndromes: clinical challenges. Pathophysiology Marco Metra Cardiology, Dept. Of experimental and applied medicine. University of Brescia. Italy
DECLARATION OF CONFLICT OF INTEREST Received honoraria from Bayer, Corthera, Novartis
Causes of Acute Heart Failure (ESC 2008) Acute decompensation of pre-existing chronic HF Acute coronary syndromes With large areas of myocardial ischaemia or infarction AMI mechanical complications RV infarction Hypertensive crisis Acute arrhythmias Valvular regurgitation Endocarditis, rupture of chordate tendinae Worsening of pre-existing VR Severe aortic valve stenosis Acute myocarditis Post-partum cardiomyopathy Tako-Tsubo cardiomyopathy Aortic dissection Cardiac tamponade Pulmonary embolism High otput syndromes Septicemia Thyrotoxicosis Severe anaemia Shunt syndromes Metra, Brutsaert, Dei Cas, Gheorghiade. ESC Intensive Acute Cardiac Care textbook
Metra, Brutsaert, Dei Cas, Gheorghiade. ESC Intensive Acute Cardiac Care textbook
Patient Comorbidities in ADHERE Patient comorbidities % of patients Insulin treated diabetes 16.6 Non insulin treated diabetes 24.9 Hypertension 70.9 Atrial arrhythmia 30.8 Ventricular arrhythmia 5.5 Previous cerebrovascular accident or TIA 15.5 Liver disease 1.6 Chronic kidney disease 19.6 Chronic pulmonary disease 27.6 Peripheral vascular disease 13.6 Anemia 17.6 Fonarow, G. C. et al. Arch Intern Med 2008;168:847-854.
Factors influencing clinical presentations & prognosis of AHF Fluid overload Blood pressure (peripheral perfusion) Myocardial ischemia Kidney dysfunction Each may or may not be present, with different relative importance, in each patient
Factors influencing clinical presentations & prognosis of AHF Fluid overload Blood pressure (peripheral perfusion) Myocardial ischemia Kidney dysfunction Each may or may not be present, with different relative importance, in each patient
Spectrum of AHFS pathophysiological mechanisms Main mechanism of onset Main cause of symptoms Vascular (peripheral / diastolic) afterload and/or predominant LV diastolic dysfunction Fluid redistribution to the lungs Cardiac (central/ systolic) contractility Sodium and water renal retention Fluid accumulation Gain in body weight No Yes Onset Rapid (hours) Gradual (days) Main symptom Dyspnoea Fatigue Systolic BP Normal to high Normal to low LV filling pressure High In a few cases may be low with CO LVEF & Cardiac output Normal Low Metra, Brutsaert, Dei Cas, Gheorghiade. ESC Intensive Acute Cardiac Care textbook
Pathophysiologic mechanisms in acute heart failure LV afterload Cardiac dysfunction systolic diastolic Metra, Brutsaert, Gheorghiade, Dei Cas. ESC Intensive Acute Cardiac Care textbook
Pathophysiologic mechanisms in acute heart failure LV afterload Cardiac dysfunction systolic diastolic Fluid redistribution to the lungs Lung congestion LV wall stress Metra, Brutsaert, Gheorghiade, Dei Cas. ESC Intensive Acute Cardiac Care textbook
Pathophysiologic mechanisms in acute heart failure LV afterload CO / LVEDP Cardiac dysfunction systolic diastolic End-organ hypoperfusion venous pressure Renal changes / renal dysfunction Fluid redistribution to the lungs Lung congestion LV wall stress Neurohormonal activation RAA SNS - ADH Inflammatory activation Na-H 2 O retention Congestion LV preload Metra, Brutsaert, Gheorghiade, Dei Cas. ESC Intensive Acute Cardiac Care textbook
tachycardia coronary perfusion pressure Myocardial ischemia MVO 2 Pathophysiologic mechanisms in acute heart failure 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, Gheorghiade, Dei Cas. ESC Intensive Acute Cardiac Care textbook
Changes in epad Systolic heart failure Diastolic heart failure Circulation 2008;118:1433-1441
Probability of an HF event 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;3:580-587
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 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0 Patients at risk NT-ProBNP: P<0.0001 Discharge NT-ProBNP <6078 Discharge NT-ProBNP >6078 0 90 180 270 360 Days Patients at risk NT-prBNP: P<0.0001 Discharge NT-ProBNP <3275 Discharge NT-ProBNP >3275 < 6078 76 69 69 42 32 <3275 57 46 28 24 19 > 6078 31 29 20 11 6 >3275 50 25 15 11 7 0.2 0 0 90 180 270 360 Days Metra Dei Cas. Eur J Heart Fail. 2007;9:776-86.
Cumulative Number of HF Hospitalizations CHAMPION: Wireless PA monitoring in HF: a randomised controlled trial. 260 240 Treatment Control 220 200 180 p < 0.001, based on Negative Binomial Regression 160 140 120 100 80 60 40 20 6 Months 15 Months 0 0 90 180 270 360 450 540 630 720 810 900 At Risk Treatment 270 262 244 209 168 130 107 81 28 5 1 Control 280 267 252 215 179 138 105 67 25 10 0 Days from Implant Abraham WT et al. Lancet. 2011 Feb 19;377(9766):658-66.
Weight changes after HF hospitalization are predictive of subsequent re-hospitalization but not of mortality: results from EVEREST Blair, J. E.A. et al. Eur Heart J 2009 30:1666-1673
Factors influencing clinical presentations & prognosis of AHF Fluid overload Blood pressure (peripheral perfusion) Myocardial ischemia Kidney dysfunction Each may or may not be present, with different relative importance, in each patient
Clinical significance of high blood pressure in AHF Cause of AHF Afterload mismatch Consequence of AHF neurohormonal activation cardiac function
SBP in AHF Registries ADHERE, AHJ 2005 107 362 patients from 282 hospitals Mean SBP, 144 mmhg SBP >140: 50% of pts OPTIMIZE-HF, JAMA 2006 48 612 patients from 259 hospitals Mean SBP, 143+33 mmhg SBP >140: 50% of pts Italian Survey, EHJ 2006 2807 patients from 206 cardiology centers Mean SBP, 141+37 mmhg, 138+36 WHF, 146+36 de novo SBP >140: 43%; 38% WHF, 49% de novo EFICA, EJHF 2006 599 patients from 60 centers Mean SBP, 126+39 mmhg; 139 without CS pts Courtesy of M. Gheorghiade
In-Hospital Mortality Rates by Admission Systolic Blood Pressure Deciles (n = 48 567) Gheorghiade, M. et al. JAMA 2006;296:2217-2226.
Risk Stratification Data Points in ED Patients With Suspected Acute Heart Failure Peacock, W. F. et al. J Am Coll Cardiol 2010;56:343-351
Acute HF treatment strategy according to SBP Oxygen /NIV, loop diuretic + vasodilator Clinical evaluation SBP >100 mmhg SBP 90-100 mmhg SBP <90 mmhg Vasodilator (NTG, nitroprusside, nesiritide), levosimendan Vasodilator and/or inotrope (dobutamine, PDEI, levosimendan) Consider preload correction with fluids or inotrope (dopamine) Good response stabilize & initiate oral diuretics, ACEI/ARB, β-blocker Poor response inotrope, vasopressor, mechanical support, consider PAC ESC 2008 guidelines
Influence of baseline blood pressure on symptoms improvement with relaxin in AHF Pre-Relax-AHF study Teerlink et al. Eur Heart J 2009 ; 30 ( Abstract Supplement ), 164
tachycardia coronary perfusion pressure Myocardial ischemia MVO 2 Pathophysiologic mechanisms in acute heart failure 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, Gheorghiade, Dei Cas. ESC Intensive Acute Cardiac Care textbook
Factors influencing clinical presentations & prognosis of AHF Fluid overload Blood pressure (peripheral perfusion) Myocardial ischemia / damage Kidney dysfunction Each may or may not be present, with different relative importance, in each patient
AHF Hemodynamic abnormalities + neurohormonal activation Low CO / hypotension LVEDP / wall stress Heart rate Inotropic agents Coronary perfusion Pulmonary congestion O 2 uptake myocardial VO 2 Myocardial damage / necrosis Metra, Brutsaert, Dei Cas, Gheorghiade. ESC Intensive Acute Cardiac Care textbook
Prevalence of Detectable (>0.01 pg/ml)troponin T in patients with AHF with daily blood sampling 46% Coronary artery disease 26% Idiopathic dilated cardiomyopathy 26% TnT (1 sample) TnT (>1 sample) No TnT 28% 60% TnT (1 sample) TnT (>1 sample) No TnT 14% Metra et al., Eur J Heart Fail. 2007;9:776-86
Prediction of Cardiac Death: CART analysis 107 patients discharged after AHF P<0.0001 NT-proBNP <6078pg/mL n= 76; 1-year survival, 91% NT-proBNP >6078 pg/ml n= 31; 1-year survival, 34% P=0.021 NYHA class I/II n= 61; 1-year survival, 95% NYHA class III/IV n= 15; 1-year survival, 71% P=0.018 ctnt undetectable n= 40; 1-year survival, 100% ctnt detectable n= 21; 1-year survival, 78% Metra et al., Eur J Heart Fail. 2007;9:776-86
Fraction of patients Freedom from Death or CV Hospitalization and ctnt plasma levels in Acute Heart Failure Fraction of patients 1 Cardiac mortality Cardiac mortality or CV hospitalizations 1 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0 P<0.0001 No ctnt detectable ctnt detectable 0 90 180 270 360 Days P<0.01 No ctnt detectable ctnt detectable Patients at risk Patients at risk: No ctnt 56 55 44 35 33 No ctnt 56 44 30 26 21 ctnt 51 34 21 15 11 ctnt 51 23 11 9 4 Metra et al., Eur J Heart Fail. 2007;9:776-86 0.2 0 0 90 180 270 360 Days
Usefulness of both BNP and Cardiac Troponin Levels to Predict In-Hospital Mortality in ADHERE Fonarow et al. Am J Cardiol 2008; 101: 231-237
Post-discharge mortality and HF readmissions in patients subdivided on the basis of troponin and BNP at discharge Xue Y et al. Eur J Heart Fail 2011;13:37-42
Factors influencing clinical presentations & prognosis of AHF Blood pressure (peripheral perfusion) Fluid overload Myocardial ischemia Kidney dysfunction Each may or may not be present, with different relative importance, in each patient
Potential impact of kidney dysfunction on outcomes of patients with AHF length of hospitalization Need of higher furosemide doses Contraindication to ACEi/ ARBs neurohormonal activation & inflammatory activity Anemia
Kidney dysfunction in heart failure
The Cardio-Renal Syndrome Gheorghiade, M. et al. J Am Coll Cardiol 2009;53:557-573
The effect of an increase in cystatin C on mortality in patients with a small rise in creatinine during hospitalization for acute heart failure. 48% Creat>0.3 mg/ Cys-C>0.2 Cys-C<0.2, / Creat<0.3 Cys-C >0.2 Lassus J P et al. Eur Heart J 2010;31:2791-2798
Mortality and/or Heart Failure Hospitalization in ADHF Patients Without Advance Kidney Dysfunction Beta trace protein Cystatin C Manzano-Fernandez, S. et al. J Am Coll Cardiol 2011;57:849-858
Clinical outcome of renal tubular damage in chronic heart failure Damman K et al. Eur Heart J 2011;eurheartj.ehr190
Pathophysiology of AHF Cardiac dysfunction Blood pressure Fluid overload Neuro-hormonal (& Inflammatory?) activation Myocardial ischemia Kidney dysfunction
Event-free survival Development of Circulatory-Renal limitations (CRLimit) to ACE inhibitors identifies patients with severe heart failure and early mortality 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 149 30 120 22 90 66 CR Limit, no inotropes, n=45 16 CR Limit, on inotropes, n=14 On ACEi, n=173 0.2 0.1 0.0 I 3 CRLimit vs. on ACE: HR, 2.8 (1.8 to 4.4; p<0.0001) adjusted for age, SBP, creatinine Inotropes vs. no inotropes: p=0.0002 I I I I I I I I I I I I I 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Months from hospitalization 46 32 31 12 7 5 3 1 10 Kittleson, M. et al. J Am Coll Cardiol 2003;41:2029-2035
Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET HR, 1.59; 95%CI, 1.28 1.98 HR, 1.30; 95%CI, 1.02 1.66 Metra et al., Eur J Heart Fail 2007; 9:901 909
Carvedilol use at discharge after a HF hospitalization is associated with improved survival: an analysis from OPTIMIZE-HF Fonarow et al. Am Heart J 2007;153:82.e1282.e11
Biomarkers in patients admitted for HF and/or acute dyspnea No. NPs ctni CgA CRP Low ly% Zairis, 2010 577 X X X Alonso-Martines, 2002 76 X Mueller,2 006 214 X Milo-Cotter, 2010 201 X Pascual-Figal, 2011 107 X X X Januzzi, JACC 2007 593 X X Manzano-Fernandez, 2011 447 X Rehman et al. JACC 2008 577 X X X Shah, 2010 134 X van Kimmenade, 2006 599 X Dieplinger et al., 2010 251 X X X ST2
Association of a low lymphocyte ratio to a poor survival: analysis from Pre-RELAX-AHF Milo-Cotter et al. Cardiology 2010; 117:190-6
Multimarker Testing with ST2 and BNP and Rates of Death After Acute Heart Failure Rehman, S. U. et al. J Am Coll Cardiol 2008;52:1458-1465
Knowing the pathophysiology of AHFS, i.e. transforming an iceberg in a mountain we can safely climb