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Hfpef
- 1. Heart Failure with Preserved Ejection Fraction Birju Patel, MD MPH
- 2. Key points • Relatively recent 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 – EDPVR) • Especially fragile exercise capacity, fatigue, DOE • Unclear how it happens, comorbidities likely key • No tx strategy for HFREF has worked in HFPEF
- 3. Terminology Energy CAD Structure / function Cardiomyopathy Usually reserved for genetic pathologies, excluding ischemic, valvular, hypertensive etiologies Dilated (eccentric), hypertrophic (concentric), or restrictive Congestive heart failure syndrome HFREF Systolic +/- diastolic dysfunction HFPEF Diastolic but no systolic dysfunction Electrical Arrhythmia ~2005 ICD 9 – 1975 ICD 10 – 1990 pathology clinical physiology clinical
- 4. Terminology Energy CAD Structure / function Cardiomyopathy Usually reserved for genetic pathologies, excluding ischemic, valvular, hypertensive etiologies Dilated (eccentric), hypertrophic (concentric), or restrictive Congestive heart failure syndrome HFREF Systolic +/- diastolic dysfunction HFPEF Diastolic but no systolic dysfunction Electrical Arrhythmia ~2005 ICD 9 – 1975 ICD 10 – 1990 pathology clinical physiology clinical Key point 1A The term HFPEF is relatively new
- 5. Working definition • Clinical diagnosis of congestive heart failure Framingham criteria – 2 major or 1 major + 2 minor • Ejection fraction normal (>50%) • No consensus here in US on need for DD or hypertrophy 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!
- 6. HPI Working definition • Clinical diagnosis of congestive heart failure Framingham criteria – 2 major or 1 major + 2 minor • Ejection fraction normal (>50%) • No consensus here in US on need for DD or hypertrophy 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 PE Imaging Empiric! Key point 1B HFPEF = CHF + EF>50
- 8. Increasing proportion of HFPEF Owan TE et al. N Engl J Med 2006;355:251-259.
- 9. Increasing proportion of HFPEF Key point 2A Half of all CHF is HFPEF Owan TE et al. N Engl J Med 2006;355:251-259.
- 10. Admissions for HFPEF vs HFREF ¼ of CHF discharges are readmitted within 30d Mortality is high post-discharge Owan TE et al. N Engl J Med 2006;355:251-259.
- 11. Significant mortality in HFPEF Mean age 74, significant comorbidities including CAD, DM, HTN Owan TE et al. N Engl J Med 2006;355:251-259.
- 12. Significant mortality in HFPEF Key point 2B Significant mortality! Owan TE et al. N Engl J Med 2006;355:251-259. Mean age 74, significant comorbidities including CAD, DM, HTN
- 14. Physiologic definition • Elevated LVEDP (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
- 15. Physiologic definition • Elevated LVEDP (filling pressure) • Especially during exacerbation or exertion • Increased stiffness (LV EDPVR) Systolic dysfunction Impaired contractility Burkhoff. Heart Failure With a Normal Ejection Fraction: Is It Really a Disorder of Diastolic Function? Circulation. 2003; 107:656-658 Key point 3 Abnormal stiffness = up+left shift LV EDPVR
- 16. TTE grades of diastolic dysfunction E – Transmitral doppler of Early passive filling A – Transmitral doppler of Atrial contraction e’ – Tissue Doppler of early MV ring = Though paradoxically flips with severe DD E/A When extreme (>15), may correlate with LVEDP =E/e’ Normal G1DD G2DD G3/4DD Nagueh. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. J Echocardiography. 2008.
- 17. 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
- 18. 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 Key point 4 People with HFPEF have poor exercise tolerance
- 19. Pathogenesis What mediates stiffening / fibrosis? No theory is definitive, but many acknowledge high burden of comorbidities One way to review is to use an anatomic approach to disease: • Cardiac • Interstitial • Cardiomyocyte • Non-cardiac • Vasculature • Skeletal muscle
- 20. Microvascular inflammation endothelium cardiomyocyte interstitial fibrosis cardiomyocyte stiffening Paulus. A Novel Paradigm for Heart Failure with Preserved Ejection Fraction. 2013; 62(4)
- 21. Inside the cardiomyocyte Kavita Sharma, and David A. Kass Circulation Research. 2014;115:79-96
- 22. Non-cardiac mechanisms Kavita Sharma, and David A. Kass Circulation Research. 2014;115:79-96
- 23. Non-cardiac mechanisms Key point 5 No definitive pathogenesis. Comorbidities likely key
- 24. Does treatment modify outcomes? Beta blocker ACEi/ARB Aldosterone Ant Digoxin ISDN/hydralazine Statin .5 .75 1 1.5 ORFavors tx Favors control HFREF OR .5 .75 1 1.5 Favors tx HFPEF Favors control Copernicus Comet Merit-HF SOLVD CHARM Added CHARM Alt Val-HEFT EMPHASIS EPHESUS RALES DIG A-HeFT CORONA GISSI-HF SENIORS OPTIMIZE OPTIMIZE PEP-CHF I-PRESERVED CHARM Preserved OPTIMIZE TOPCAT DIG Ancillary GISSI-HF Also, phase 3 for neprilysin inhibitor pending
- 25. Does treatment modify outcomes? Beta blocker ACEi/ARB Aldosterone Ant Digoxin ISDN/hydralazine Statin .5 .75 1 1.5 ORFavors tx Favors control HFREF OR .5 .75 1 1.5 Favors tx HFPEF Favors control Copernicus Comet Merit-HF SOLVD CHARM Added CHARM Alt Val-HEFT EMPHASIS EPHESUS RALES DIG A-HeFT CORONA GISSI-HF SENIORS OPTIMIZE OPTIMIZE PEP-CHF I-PRESERVED CHARM Preserved OPTIMIZE TOPCAT DIG Ancillary GISSI-HF Key point 6 No treatment significantly alters cardiac events in HFPEF
- 26. Key points • Relatively recent 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