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HFPEF
This document discusses heart failure with preserved ejection fraction (HFpEF), formerly known as diastolic heart failure. It provides background on HFpEF versus systolic heart failure and explores the pathophysiology and management of HFpEF. Key points include: 1) HFpEF is a distinct clinical syndrome from heart failure with reduced ejection fraction (HFrEF), with normal ejection fraction but evidence of diastolic dysfunction. 2) Impaired systolic function can be detected in HFpEF patients using strain imaging, despite preserved global ejection fraction. 3) The pathophysiology of HFpEF is complex and multifactorial, involving microvascular inflammation, cardiomyocyte stiff
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HFPEF
- 1. Heart Failure with PreservedEjection Fraction Gopal C Ghosh
- 2. Yancy et al.2013 ACCF/AHA Heart Failure Guideline
- 3. HFpEF vs DiastolicHeart Failure What’s in a Name? • Patient with HF -----> minimal diastolic dysfunction • Diastolic dysfunction features --- > but no HF (Hypertensive heart disease) • Key non-diastolic features such as limited systolic reserve, abnormal volume regulation, and maladaptive ventricular–arterial interaction • In other words, a normal-range EF did not imply normal systolic function
- 4. Figure : AverageLongitudinal and Circumferential Systolic StrainAverage longitudinal strain (red bars) and circumferential systolic strain (green bars) among normal controls (n = 50), hypertensive heart disease (HHD) patients (n = 44), heart failure with pre... Impaired Systolic Function by Strain Imaging in Heart Failure With Preserved Ejection Fraction Journal of the American College of Cardiology, Volume 63, Issue 5, 2014, 447–456
- 5. Impaired Systolic Functionby Strain Imaging in Heart Failure With Preserved Ejection Fraction • Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome • Frankly elevated filling pressure based on an E/E’ ratio 15 or more was present in only 49% of the patients
- 6. Scheme for diagnosisof heart failure with preserved ejection fraction Michel Komajda, and Carolyn S.P. Lam Eur Heart J 2014;35:1022-1032 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com
- 7. Working definition • Clinicaldiagnosis of congestive heart failure Framingham criteria – 2 major or 1 major + 2 minor Ejection fraction normal (>50%) • No consensus in US on need for DD or hypertrophy • No significant valvular abnormalities by echocardiography Major Minor PND or orthopnea DOE Rales Nocturnal cough HJR Tachycardia S3 Ankle edema JVD (or elevated CVP) Hepatomegaly CXR pulmonary edema CXR engorged pulm vessels Cardiomegaly Pleural effusion 10lb weight loss with diuretics Decreased vital capacity HPI PE Imaging Empiric! Yancy et al. 2013 ACCF/AHA Heart Failure Guideline
- 8. Arguments for heartfailure with preserved ejection fraction as a transitory stage to heart failure with reduced ejection fraction (left) vs. heart failure with preserved ejection fraction as a distinct entity from heart failure with reduced ejection fraction (right). Michel Komajda, and Carolyn S.P. Lam Eur Heart J 2014;35:1022-1032 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com
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- 10. • The mortalityrate among patients with diastolic heart failure ranges from 5 to 8 percent annually, as compared with 10 to 15 percent among patients with systolic heart failure • Heart failure developed within five years in 11 to 15 percent of persons older than 65 years of age who had no clinical evidence of heart disease but had Doppler evidence of left ventricular diastolic dysfunction Aurigemma GP et al: The Cardiovascular Health Study. J Am Coll Cardiol 2001;37:1042-1048
- 12. Increasing proportion ofHFpEF Owan TE et al. N Engl J Med 2006;355:251-259.
- 14. Admissions for HFPEFvs HFREF Owan TE et al. N Engl J Med 2006;355:251-259.
- 15. Mortality for patientswith HF-PEF (heart failure with preserved left ventricular ejection fraction) and HF-REF (heart failure with low left ventricular ejection fraction), adjusted for age, gender, aetiology of heart failure, hypertension, diabetes, atrial fibrillation. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) Eur Heart J 2012;33:1750-1757 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2011. For permissions please email: journals.permissions@oup.com
- 16. CONTs...... • Hong Kong:HFpEF accounts for 67% of HF admissions • Clinical outcome same as HFrEF (Inhospital, 30 days & 1 year mortality) • 40% of deaths are non-cardiac Yip GW et al. Am J Cardiol. 1999;84:563–567 Sharma K et al. Circulation Research.2014; 115: 79-96
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- 18. Physiologic definition • ElevatedLVEDP (filling pressure) • Especially during exacerbation or exertion • Increased stiffness (LV EDPVR) Systolic dysfunction Impaired contractility Diastolic dysfunction Impaired relaxation Higher LVEDP Burkhoff. Heart Failure With a Normal Ejection Fraction: Is It Really a Disorder of Diastolic Function? Circulation. 2003; 107:656-658
- 20. Poor exercise tolerance– fatigue and DOE • Why does exercise make anyone tired? • VO2max ~ CO x O2 extraction • Ventilation/lactate threshold • Normally CO increases with HR, SV, contractility while simultaneously decreasing stiffness to improve filling to match needs • In HFPEF, HR limits diastolic filling time, stiffness (EDPVR) paradoxically worsens Larger LVEDP necessary, causes DOE Limited HR and limited LVEDV results in non-optimal use of Frank-Starling curve, reduces CO (and thus VO2max) and causes fatigue Abudiab. Cardiac Output Response to Exercise in Relation to Metabolic Demand in heart Failure with Preserved Ejection Fraction. Eur J Heart Fail. 2013; (15):776-785
- 21. Pathogenesis What mediates stiffening/ fibrosis? No theory is definitive, but many acknowledge high burden of comorbidities
- 22. Microvascular inflammation endothelium cardiomyocyte interstitial fibrosis cardiomyocytestiffening Paulus. A Novel Paradigm for Heart Failure with Preserved Ejection Fraction. 2013; 62(4)
- 23. Inside the cardiomyocyte KavitaSharma, and David A. Kass Circulation Research. 2014;115:79-96
- 24. Non-cardiac mechanisms Kavita Sharma,and David A. Kass Circulation Research. 2014;115:79-96
- 26. HFpEF a uniformsyndrome? • HFpEF is not homogeneous, but is rather a heterogeneous condition consisting of several pathophysiological subtypes
- 28.
- 30. Hong Kong trial •150 patients with HFNEF (LVEF >45%) were randomised • QoL (Minnesota Heart Failure Symptom Questionnaire), 6-minute walk test (6MWT) and Doppler echocardiography were performed at baseline, 12, 24 and 52 weeks
- 31. Hong Kong trial •ACE(Ramipril) vs. ARB(Irbesartan) vs. diuretics Yip GWK, et al. Heart 2008;94;573-580.
- 32. PEP-CHF STUDY • 53european centres • Mean follow up 26.2 months • EF 40% or more(Or wall motion score index >1.4)
- 33. Kaplan–Meier curves showingtime to first occurrence of the primary endpoint, all-cause mortality or unplanned heart failure related hospitalization, for the entire duration of the study. John G.F. Cleland et al. Eur Heart J 2006;27:2338-2345 © The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
- 35. I-PRESERVE • 4128 patientswho had heart failure with a preserved ejection fraction(EF>45%) • Rates of hospitalisations were also same
- 37. CHARM PRESERVED TRIAL •n=3023; LVEF >40% • Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months
- 39. Figure Time tocardiovascular death or hospital admission for CHF Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM- Preserved Trial The Lancet, Volume 362, Issue 9386, 2003, 777 - 781
- 40. CHARM Preserved Trial CVMortality or CHF hospitalization HR 0.89 p=0.118 22.0% 24.3% 0% 10% 20% 30% Candesartan Placebo 11.2% 11.3% 0% 5% 10% 15% Candesartan Placebo European Society of Cardiology 2003 CV Mortality HR 0.99 p=0.918
- 42. VALIDD Trial: supportingantihypertensive Tx Valsartan In Diastolic Dysfunction Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used. Solomon SD. Lancet 2007; 369: 2079–87
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- 44. From: Clinical Effectivenessof Beta-Blockers in Heart Failure: Findings From the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) Registry J Am Coll Cardiol. 2009
- 45. OPTIMIZE – HF:Betablockers Hernandez, et al. JACC. 2009 Jan 13;53(2):184-92 Diastolic heart failure Systolic heart failure
- 46.
- 47. Trial profile. Marcus D.Flather et al. Eur Heart J 2005;26:215-225 European Heart Journal vol. 26 no. 3 © The European Society of Cardiology 2005; all rights reserved.
- 48. SENIORS: Nevibolol Study ofthe Effects of Nebivolol Intervention on Outcomes and Hospitalisation in Seniors with Heart Failure) Ghio S, et al. Eur Heart J. 2006;27: 562–568
- 49.
- 50. SWEDIC: Carvedilol Bergstrom A.Eur J Heart Fail. 2004;6:453-61. Swedish Doppler-echocardiographic study
- 51. ALDO-CHF • Men andWomen aged >50 years , had current heart failure symptoms consistent with New York Heart Association (NYHA) class II or III, left ventricular ejection fraction (LVEF) of 50% or greater • ECHO evidence of diastolic dysfunction
- 52. Date of download:3/13/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction: The Aldo-DHF Randomized Controlled Trial JAMA. 2013;309(8):781-791. doi:10.1001/jama.2013.905 Error bars indicate 95% CI. P values describe comparisons of the changes in the placebo or spironolactone group at the respective time point vs baseline. No further improvement by spironolactone occurred between the 6-month and 12-month visits (P = .39 for E/e′). Figure Legend:
- 53. TOPCAT • Patients 50years of age or older • Clinically defined signs and symptoms • Left ventricular ejection fraction of 45% or more • Spironolactone 15-45 mg
- 54. Incidence Rates ofthe Primary Composite Outcome, Its Components, and Additional Secondary Outcomes Pitt B et al. N Engl J Med 2014;370:1383-1392.
- 55. Kaplan–Meier Plots of TwoComponents of the Primary Outcome
- 56. RAAM PEF-EPLERENONE • Exercisecapacity- improves • Markers of collagen turnover-decreased • Diastolic function- improves • DIG-PEF trial • RELAX trial
- 57.
- 58. Figure : Kaplan-Meiersurvival and survival without cardiovascular (CV) hospitalization in propensity-matched patients grouped by statin therapy. Hidekatsu Fukuta et al. Circulation. 2005;112:357-363 Copyright © American Heart Association, Inc. All rights reserved.
- 59. Role of NO—cyclicguanosine 3′,5′-monophosphate (cGMP)—protein kinase-G activity (PKG) pathway in heart failure with preserved ejection fraction. Michel Komajda, and Carolyn S.P. Lam Eur Heart J 2014;35:1022-1032 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com
- 60. Key points • Relativelyrecent term, HFPEF = clinical dx of CHF + preserved EF • Half of all CHF, just as lethal • Characterized by abnormal stiffness (up+left shift of LV end diastolic pressure-volume relationship – LV EDPVR) • Especially fragile exercise capacity, fatigue, DOE • Unclear how it happens, comorbidities likely key • No tx strategy for HFREF has worked in HFPEF