Diagnosis is it really Heart Failure?

ESC Congress Munich - 25-29 August 2012 Heart Failure with Preserved Ejection Fraction From Bench to Bedside Diagnosis is it really Heart Failure? Prof. Burkert Pieske Department of Cardiology Med.University of Graz

Diagnosis of HFpEF Signs and Symptoms of HF Preserved EF Evidence of Diastolic Dysfunction Exclusion of non-cardiac causes

Diagnosis of HFpEF Signs and Symptoms of HF Preserved EF Evidence of Diastolic Dysfunction Exclusion of non-cardiac causes

HFPEF Is it really Heart Failure? 1. How to diagnose HFPEF current standards 2. CV abnormalities beyond diastole 3. Role of comorbidities

How to diagnose HFPEF? Standard approaches: a) HFPEF = Heart Failure + EF 40/45/50% ( Mega-Trial- Approach ) b) HFA/ESC-Criteria 2007 c) EAE/ASE-Criteria 2009 d) New ESC HF Guidelines 2012

I-Preserve Echo Substudy

I-Preserve Echo Substudie I-Preserve included 4128 patients with HFPEF Inclusion criteria: Age 60 years, EF 45%, recent Heart Failure hospitalisation or moderate/severe symptoms + 1 sign (pulmonary congestion; LBBB; Echo: increased wall thickness; LA enlargement Echo-Substudy: 745 patients with 2D, Doppler- and tissue doppler analyses at randomisation

Structural LV Remodeling Almost 50%: no structural LV Remodeling! Zile et al.; Circulation 2011; 124

LA-Remodeling & Diastol. function 1/3: No LA-Remodeling! 1/3: normal diastolic function! Zile et al.; Circulation 2011; 124

Remodeling and Prognosis I-Preserve Echo Substudy: Objective evidence of remodeling/diastolic dysfunction = more heart failure endpoints! LV Hypertrophy LA Dilatation Diastolic Dysfunction Zile M et al.; Circulation 2011; 124: 2491-2501

HFA/ESC Recommendations Paulus W et al., Eur Heart J 2007; 2539-2550

HFA/ESC Recommendations: Diagnosis 1. Signs and/or Symptoms of Heart Failure 2. Preserved global systolic LV Function (EF>50%) 3. Indices of abnormal LV relaxation, filling, compliance or stiffness 4. BNP or NTproBNP

Diagnosis: Diastolic Heart Failure HFA/ESC 2007 Paulus W et al.

Diagnosis: Diastolic Heart Failure HFA/ESC 2007 Paulus W et al.

E/é and LVEDP Little et al.; Circulation 2009; 120: 802-809

Diagnosis: Diastolic Heart Failure HFA/ESC 2007 Paulus W et al.

NTproBNP in I-Preserve Baseline plasma NT-proBNP and clinical characteristics: results from the irbesartan in heart failure with preserved ejection fraction trial. McKelvie RS, Komajda M, McMurray J, Zile M, Ptaszynska A, Donovan M, Carson P, Massie BM; I-Preserve Investigators. Majority in NYHA III Median NTproBNP: 341 (135-974) pg/ml No Atrial fibrillation: around 250 pg/ml (ca. 75%) With atrial fibrillation: >900 pg/ml (ca. 25%)

ESC 2012: Diagnosis of HF ESC Heart Failure Guidelines 2012

Objective evidence of cardiac dysfunction ESC Guidelines 2012

Echo parameters of diastolic dysfunction ESC Guidelines 2012

Diagnosis: HFPEF Change in Paradigms 2012: New Echo Techniques & Parameters Stress tests ( Diastolic Stress Test )! New Biomarkers: Subgroups, Response to Therapy

New Echo Techniques Strain rate imaging & Diastolic stress test Left atrial strain Rotation, Twist & Untwist Oh JK et al., Circulation Cardiovasc Imaging 2011;444-455

Diastolic stress test Borlaug et al.; Circ Heart Fail 2010; 3: 588-595

Diastolic stress test Borlaug et al.; Circ Heart Fail 2010; 3: 588-595

Diagnostic accuracy of exercise PASP Borlaug et al.; Circ Heart Fail 2010; 3: 588-595

HFPEF - Diagnosis There are no generally accepted diagnostic criteria Large Mega-Trials may have included patients without cardiac origin of symptoms The diastolic stress test and novel imaging parameters may improve diagnostic accuracy

HFPEF Is it really Heart Failure? 1. How to diagnose HFPEF current standards 2. CV abnormalities beyond diastole 3. Role of comorbidities

Ventricular Dysfunction Impaired relaxation Impaired filling Systolic Dysfunction Atrial dysfunction Autonomic dysfunction Chronotropic incompetence Vascular dysfunction Vascular stiffening Ventriculo-arterial coupling Heart failure with preserved EF Elevated blood pressure Inadequate BP response to exercise Pulmonary hypertension Valvular disease Dynamic mitral regurgitation

Yu CM et al., Circulation 2002; 105:1195-1201 Systolic dysfunction in HFPEF 339 participants: 92 SHF (EF<50%), 73 DHF (EF>50%), 68 isolated diastol. dysfunction, 106 normals; 52% of DHF with systolic abnormalities. TDI long axis fibre shortening

LA contractile dysfunction No increase in LA contractile function (assessed by tissue doppler mitral annular A wave velocity) in HFprEF during stress Melenovsky et al., J Am Coll Cardiol 2007; 49(2)

Chronotropic incompetence HFprEF (n=17) and matched controls (n=19): maximal effort upright cycle ergometry & radionuclide-ventriculography Matched workloads: Reduced chronotropic, vasodilator, and cardiac output reserve during exercise Borlaug et al., Circulation 2006; 114(20) Kitzman et al., Circulation 2008; 117

HFPEF Is it really Heart Failure? 1. How to diagnose HFPEF current standards 2. CV abnormalities beyond diastole 3. Role of comorbidities

Lung Disease COPD Iron deficiency and anemia Renal dysfunction Volume overload Heart failure with preserved EF Aging & Deconditioning Obesity & Sarcopenia Psychic Disorders Depression

Pulmonary disease & HFpEF

Lung function & Risk for heart failure Health ABC Study: 3075 participants, no heart failure+spirometry upon inclusion Georgiopouluo et al.; Am J Med 2011; 124(4): 34-341

Prevalence of COPD in HFpEF Hawkins et al.; Eur J Heart Fail 2009; 11: 130-139

Chronic kidney disease Chronic kidney disease impacts on LV remodeling Cerasola et al.; J Nephrol 2011; 24(01): 1-10

Chronic kidney disease & Diastole Chronic kidney disease negatively impacts on diastolic function Cerasola et al.; J Nephrol 2011; 24(01): 1-10

Comorbidities & Incident HF Factor HR (95% CI)* P value* Cut-off percentile Cut-off value Points Creatinine 1.21 (1.01 1.45) 0.036 >75 th percentile > 92.8 μmol/l 1 FEV1:FVC 1.21 (1.02 1.43) 0.029 <25 th percentile < 91 % predicted 1 Hemoglobin 1.24 (1.09 1.40) <0.001 <25 th percentile < 13 g/dl 1 *Hazards ratio are for 1SD increase in serum creatinine, 1SD decrease in FEC1:FVC ratio and 1 unit decrease in hemoglobin concentration, adjusting for age, sex, body mass index, systolic blood pressure, hypertension treatment, cholesterol, diabetes mellitus, prior myocardial infarction, valvular heart disease, and left ventricular systolic and diastolic function Lam C.S. et al Circulation 2011

Comorbidities and NYHA class Edelmann et al.; Clin Res Cardiol 2011; 100: 755-764

Ventricular Dysfunction Impaired relaxation Impaired filling Systolic Dysfunction Lung Disease COPD Iron deficiency and anemia Atrial dysfunction Autonomic dysfunction Chronotropic incompetence Vascular dysfunction Vascular stiffening Ventriculo-arterial coupling Heart failure with preserved EF Renal dysfunction Volume overload Aging & Deconditioning Obesity & Sarcopenia Elevated blood pressure Inadequate BP response to exercise Pulmonary hypertension Valvular disease Dynamic mitral regurgitation Psychic Disorders Depression

Summary HFPEF is a heterogeneous syndrome Patients need to be classified according to the underlying pathophysiology and CV phenotypes Co-morbidities have to be taken into account Specific etiologies need to be excluded In clinical practice, we often deal with a mixed picture of cardiac and extracardiac abnormalities that sum up to HFPEF