ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΜΕ ΔΙΑΤΗΡΗΜΕΝΟ ΚΛΑΣΜΑ ΕΞΩΘΗΣΗΣ

Transcription

1 ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΜΕ ΔΙΑΤΗΡΗΜΕΝΟ ΚΛΑΣΜΑ ΕΞΩΘΗΣΗΣ ΙΓΝΑΤΙΟΣ ΟΙΚΟΝΟΜΙΔΗΣ MD, PHD, FESC ΑΝΑΠΛΗΡΩΤΗΣ ΚΑΘΗΓΗΤΗΣ ΚΑΡΔΙΟΛΟΓΙΑΣ Β ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ, ΕΘΝΙΚΌ ΚΑΙ ΚΑΠΟΔΙΣΤΡΙΑΚΌ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΝΟΣΟΚΟΜΕΙΟ ΑΤΤΙΚΟΝ

2 HFPEF: definition ESC 2005 A diagnosis of primary diastolic heart failure requires three obligatory conditions to be simultaneously satisfied: (1) presence of signs or symptoms of congestive heart failure; (2) presence of normal or only mildly abnormal left ventricular systolic function; (3) evidence of abnormal left ventricular relaxation, filling, diastolic distensibility or diastolic stiffness ESC 2012 ACC/AHA 2013 HF definition HFPEF definition Abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate commensurate with the requirement of the metabolizing tissues, despite normal filling pressure (or only at the expense of increased filling pressures) Requires 4 conditions to be satisfied Typical symptoms of HF Typical signs of HF Preserved ejection fraction (EF 45%) and left ventricle not dilated Relevant structural heart disease and/or diastolic dysfunction Complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood Stage C heart failure Known structural heart disease Typical signs and symptoms Preserved ejection fraction (EF 50% HF-PEF, EF 41% 50% borderline HF-PEF)

3 In Epidemiology studies among subjects without HF, 28.1% have some degree of LV diastolic dysfunction 70% in HfpEF worsening of LV diastolic dysfunction is associated with an increased risk of developing HF JAMA 2003; 289:194 JAMA 2011; 306:856.

4 Heterogeneity of HFPEF in Registries and RCTs Registries RCTs LVEF at inclusion 40%, > 50% 40%, >45%, 50% Mean LVEF 58% - 62% 55% - 67% Median NT-proBNP 602pg/ml 1840 pg/ml 158 pg/ml 887 pg/ml % Hypertension % AF % DM % CAD ADHERE OPTIMIZE Swedish HF Registry IN-HF registry PEP-CHF RELAX DIG PARAMOUNT CHARM-preserved I-Preserve TOPCAT Aldo-DHF

5 ALARM REGISTRY: LVEF % By AHF Classification 100% 80% 60% 40% 20% 0% Avg LVEF %/EHS HF II 38/38% 38/37% 39/40% 32/33% 48/44% 44/48% 44% 16% 32% 29% 33% 37% 62% 53% 44% 43% 45% 46% 31% 41% 46% 27% 25% 26% 21% 11% 17% 15% All AHF ADHF P-OE Cardiogenic HYP AHF RV AHF High output shock LVEF <30% LVEF 30-44% LVEF >=45% Sample = 3,283 AHF patients with specified LVEF value Parissis J, Ikonomidis I on behalf of the ALARM Steering Committee, Am J Cardiol

6 HFPEF: Current state of the problem A significant health problem: ~50% of all HF cases Mortality: In-hospital 3%, annual 11%, 5-y 55% Increasing hospitalization rates compared to HFREF Mortality rates higher, more similar to HFREF, after hospitalization

7 Oktay et al, Curr Heart Fail Rep 2013

8 HFPEF: causes 1. Cardiovascular risk factors: Arterial hypertension, Diabetes mellitus, Obesity, Atrial fibrillation, CAD, ageing 2. Non-cardiovascular risk factors: Renal impairment, chronic lung diseases, anemia, cancer, liver disease, peptic ulcer disease, hypothyroidism 2. Hypertophic cardiomyopathy 3. Valvular diseases 4. High-output HF (anemia, hyperthyroidism, liver disease, AV fistula) 5. Infiltrative disorders (e.g. amyloidosis, sarcoidosis) 6. Myocardial storages diseases (e.g. haemochromatosis) 7. Endomyocardial disease (e.g. radiation) Lam CS, EJHF 2010 K McDonald. Int J Cardiol 2008

9 A heterogeneous pathophysiology a heterogeneous syndrome Senni M, et al. EHJ 2014

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11 Pathophysiology of HFPEF: Diastolic dysfunction Ox stress/ NO bioavailability Stiff titin isoform Calcium overload Prolonged LV relaxation Reduced LV compliance Borlaug BA, Nat Rev Cardiol 2014

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13 CALCULATION OF LV FILLING PRESSURE OR PCWP E/A= DT= ms IVRT=70-90 ms E/A<0.75 DT>240 ms IVRT>90 ms E/A= DT= ms IVRT<90 ms E/A>1.5 DT<160 ms IVRT<70 ms Mean Ε/Ε >13 ΜEAN LVDP <15 mmhg ΜEAN LVDP =15-25 mmhg ΜEAN LVDP >25 mmhg

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15 LA Volumes Paulus W J et al. Eur Heart J 2007;28:

16 J Am Soc Echocardiogr 2016;29:

17 Diastolic stress test

18 Role of BNP/exercise in Diagnosis

19 Diastolic stress test J Am Soc Echocardiogr 2016;29:

20 DEVELOPMENT OF HF IN DIABETICS

21 VA COUPLING TO DIAGNOSE HEFPEF J Am Coll Cardiol 2013;61:

22 Doppler-Tissue Doppler Imaging Mitral annulus velocities-strain rate Technical difficulties Angle dependent Load dependent Interference-noise Time consuming analysis Great interobserver variability Any alternative?

23 Impaired Systolic Function by Strain Imaging in HFpEF 219 HFpEF patients Ιmpaired systolic function GLS, GCS despite preserved global LVEF in HFpEF Kraigher-Krainer et al. J Am Coll Cardiol 2014;63:447 56

24 Ikonomidis I et Eur J Heart Fail 2015 Diastolic suction Control ptw Δ1:33% UntwMVO Δ2:79% A A Hypertensive ptw Δ1:26 % Δ2:64 % B UntwMVO UtwEDF UtwEDF MVO MVO EDF EDF

25 Exercise capacity in hypertensives A reverse association between PWV and VO2PEAK was revealed in hypertensives with delayed BPRR Increased LV untwisting rate was associated with increased NTproBNP and reduced VO2 peak Triantafyllidi H, Ikonomidis I Blood Pressure Monit, 2013 Ikonomidis I, Eur J Heart Failure 2015

26 NORMAL Ikonomidis I Heart 2009, Circulation Cardiovasc Imaging 2014 RA no CAD

27 Healthy MV O 33 % E E F 75 % IMPAIRED GLS AND TWISTING IN R.ARTHRITIS 70 msec Ikonomidis et al Circulation Cardiovascular Imaging 2015 RA without CAD MV O 26 % EE F 64 % RA with CAD MV O 20 % EE F 50 % 85 msec 100 msec

28 Association of GLS with fibrosis in HCM Fibrosis related to risk of sudden death European Heart Journal Cardiovascular Imaging (2012) 13,

29 Apical sparing for diagnosis of c.amyloidosis vs other causes of LVH Phelan et al. Heart 2012;98: GLS= -7.8%

30 LA assessment Differentiates HT- HCM vs normal controls a c MVO v MVO c a v Paraskevaidis, Ikonomidis Heart 2008

31 LA STRAIN pre-post cardioversion

32 2D STRAIN pre-post cardioversion

33 NOVEL INDICES OF LV DIASTOLIC FUNCTION J Am Soc Echocardiogr 2016;29:

34 Predictors of rehospitalisation and CV death in HEFPEF

35 Patients with a composite of abnormal TDI indices for LV function and preserved EF had an increased mortality (survival rate 37%) compared to patients with normal TDI markers (survival rate 83%) (log rank=11,1 p=0.001,). Composite of S <8 cm/s E 8cm/sec and/or mean E/E 13 Ikonomidis I Shock 2010

36 Tissue Doppler Imaging as a Prognostic Marker for Cardiovascular Events in Heart Failure with Preserved Ejection Fraction and Atrial Fibrillation J Am Soc Echocardiogr 2010;23:

37 LA strain the strongest predictor of CV events Circulation: Cardiovascular Imaging.2016; 9: e00375

38 Incremental Value of Deformation Indices for Predicting Subsequent Reduction in EF>10% at 1year post chemotherapy ΔGLS>11% at 6m ΔGLS>10% at 3m* J Am Soc Echocardiogr 2013;26: *Heart 2010;96:701 7.

39 GLS is a strong independent predictor of all-cause mortality in patients with AOS pef GLS detects subclinical dysfunction and has incremental prognostic value over traditional risk markers including haemodynamic severity, symptom class, and LVEF in patients with AS. Independent predictor of all-cause mortality (HR: 1.38, P=0.001) Incorporation of GLS into risk models may improve the identification of the optimal timing for AV replacement. European Heart Journal Cardiovascular Imaging 2012;13:

40 Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis Figure 1. Example of Measurement of E/SReMeasurements are shown of early mitral inflow velocity (E) using pulsewave Doppler and early diastolic strain rate (SRe) from 2D speckle tracking. AVC = aortic valve closure. Jordi S. Dahlb E. Møller JACC: Cardiovascular Imaging, Volume 9, Issue 5, 2016,

41 Strain -AoRergurgitation Am J Cardiol. 2012;110(7): J Am Soc Echocardiogr. 2011;24(11): GLS 17.5 ± 3.1% before AVR >-19.5%, sens: 77%,spec:94% for progressive AR >-11.5%, impaired outcome post AVR

42 GLS predicts LV dysfunction after mitral valve repair cut-off value LV GLS 19.9% predicts long-term postoperative LV dysfunction sensitivity 90% specificity 79% A GLS of independent predictor of long-term LV dysfunction after adjustment for parameters currently implemented into guidelines. European Heart Journal Cardiovascular Imaging 2012

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44 conclusions HFpEF is a clinical diagnosis that is assisted by echocardiography evaluation The pathophysiology of the syndrome is multi-factorial and only partly understood Diuretics remain the only recommended therapy for HFpEF Encasement of CGMP,serelaxin LCZ promising results

45 Serelaxin in AHF: preserved EF vs reduced EF RELAX-AHF 1161 AHF pts SBP >125 mmhg Serelaxin, recombinant human relaxin 2, 48-hour iv or placebo Filippatos, Teerlink, Farmakis et al, Eur Heart J 2014

46 RESTRICTIVE CARDIOMYOPATHY

47 Restrictive

48 Apical sparing for diagnosis of c.amyloidosis vs other causes of LVH Phelan et al. Heart 2012;98: GLS= -7.8%

49 Increased benefit of IL-1 inhibition in RA-CAD Anakinra:IL-1ra Ikonomidis I Lekakis J. Circulation Cardiovasc Imaging 2014

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51 Phenotypes of HFPEF based on clinical presentation EXERCISE-INDUCED DIASTOLIC DYSFUNCTION Exercise intolerance NYHA II Minimal fluid retention No HF hospitalization BNP normal/mildly abn Mild Diastolic dysfunction (DD) Low PASP E/e on exercise MOST DIFFICULT TO DIAGNOSE LOWEST RISK VOLUME OVERLOAD PULMONARY HYPERTENSION/RV FAILURE Shah, SJ. JACC 2013 NYHA III Mild/moderate leg edema/rales Recent HF hospitalization Elevated BNP/NT-proBNP Moderate DD PASP moderately elevated NYHA III Severe edema/ dyspnea at rest/ascites Frequent hospitalizations Moderate/Severe DD Multivalvular lesions, RV dysfunction Most common phenotype enrolled in trials Diagnosis may be missed, especially in obese/lung disease RHC can be useful PASP significantly elevated PAH on top of pulmonary venous hypertension Highest BNP HIGHEST RISK