Guideline Management of Chronic Heart Failure 2013 ACC/AHA Guideline Mgmt HF 2016 ACC/AHA/HFSA Focused Update 2017 ACCAHA/HFSA Focused Update October 17 th, 2017 Dawn Lombardo DO, MSc Professor of Medicine/Clinical HS University of California, Irvine Medical Center Division of Cardiology/DOM Medical Director Advanced Heart Failure Program Program Director Cardiovascular Fellowship Program
Disclosures None 2
Learning Objectives: 1. Describe the evaluation of patients presenting with stable heart failure 2. Use recent guidelines to select appropriate medical therapies for patients with stable heart failure with reduced EF 3. Develop appropriate management strategies for the patient with stable heart failure with preserved EF 3
Key References 1. 2013 ACCF / AHA Heart Failure Guidelines http://content.onlinejacc.org/article.aspx?doi=10.1016/j.jacc.2013.05.019 2. 2016 ACCF/ AHA heart Failure Guidelines Update http://circ.ahajournals.org/content/circulationaha/early/2016/05/18/cir.00000 00000000435.full.pdf 1. 2010 HFSA Guidelines 4 October 107 2017
Definition of Heart Failure HFSA 2010 Practice Guideline Syndrome caused by cardiac dysfunction Neurohormonal & circulatory abnormalities Characteristic symptoms: Fluid retention Shortness of breath Fatigue, especially on exertion Physiologic description: Elevated cardiac filling pressures OR Inadequate peripheral oxygen delivery at rest or during stress caused by cardiac dysfunction 5
Definition of Heart Failure HFSA 2010 Practice Guideline HF is progressive and often fatal ****Patients can be stabilized! **** Myocardial dysfunction and remodeling may improve Spontaneously Consequence of therapy 6
Definition of Heart Failure ACC/AHA 2013 Guidelines 7
Heart Failure in the US A Growing Problem 6.6 million Americans with HF projected ~ 8 million by 2030 870,000 new HF diagnoses annually 300,000-800,000 Americans with advanced HF 1 million hospitalizations /year Deaths > 300,000 HF/year mortality remain ~ 50% at 5 years. $32 billion/year expected to rise to $70 billion by 2030 80% due to hospitalizations.
Burden of Heart Failure
Stages of Heart Failure 10
NYHA-FC and Mortality 11
Stages, Phenotypes and Treatment of Heart Failure 12
Residual Risk for HFrEF Despite Conventional GDMT 13
Heart Failure w/preserved Ejection Fraction vs Reduced Ejection Fraction HFpEF & HFrEF: A clinical syndrome characterized by breathlessness, fatigue and edema caused by an abnormality of the heart. E. Braunwald modified by B. Borlaug and M Redfield HFrEF & HFpEF Similar Signs and Symptoms HFpEF & HFrEF: Poor quality of life Premature mortality High hospitalization rates Substantial health-care resource utilization HFpEF = EF >= 50% + S/S + DD HFpEF DD DD = part of normal human aging & seen in many people who never have HFpEF DD = RF for HFpEF Edelmann, et al. 2011; Hamo, et al. 2015; Redfield MM, et al. 2017
Risk Scoring I IIa IIb III Validated multivariable risk scores can be useful to estimate subsequent risk of mortality in ambulatory or hospitalized patients with HF.
Risk Scores to Predict Outcomes in HF Risk Score Reference (from full-text guideline)/link Chronic HF All patients with chronic HF Seattle Heart Failure Model (204) / http://seattleheartfailuremodel.org Heart Failure Survival Score CHARM Risk Score (207) CORONA Risk Score (208) Specific to chronic HFpEF I-PRESERVE Score (202) Acutely Decompensated HF ADHERE Classification and Regression Tree (CART) Model American Heart Association Get With the Guidelines Score (200) / http://handheld.softpedia.com/get/health/calculator/hfss-calc- 37354.shtml (201) (206) / http://www.heart.org/heartorg/healthcareprofessional/getwiththeguidelin eshfstroke/getwiththeguidelinesheartfailurehomepage/get-with-the- Guidelines-Heart-Failure-Home- %20Page_UCM_306087_SubHomePage.jsp EFFECT Risk Score (203) / http://www.ccort.ca/research/chfriskmodel.aspx ESCAPE Risk Model and Discharge Score (215) OPTIMIZE HF Risk-Prediction Nomogram (216)
Recommendations for Biomarkers in HF Biomarker, Application Setting COR LOE Natriuretic peptides Diagnosis or exclusion of HF Prognosis of HF Ambulatory, Acute Ambulatory, Acute Achieve GDMT Ambulatory IIa B Guidance of acutely decompensated HF therapy Acute IIb C Biomarkers of myocardial injury Additive risk stratification Acute, Ambulatory I A Biomarkers of myocardial fibrosis Additive risk stratification Ambulatory Acute I I IIb IIb A A B A
Biomarkers in Heart Failure BNP (NT-proBNP) in Heart Failure Myocardial stress/strain/stretch BNP Ventricles > atria BNP elevated in HF Levels correlate with PCW and prognosis 18
Causes for Elevated Natriuretic Peptide Levels Cardiac Heart failure, including RV syndromes Acute coronary syndrome Heart muscle disease, including LVH Valvular heart disease Pericardial disease Atrial fibrillation Myocarditis Cardiac surgery Cardioversion Noncardiac Advancing age Anemia Renal failure Pulmonary causes: obstructive sleep apnea, severe pneumonia, pulmonary hypertension Critical illness Bacterial sepsis Severe burns Toxic-metabolic insults, including cancer chemotherapy and envenomation
2013 ACCF/AHA Guideline for the Management of Heart Failure
HF Risk Factor Treatment Goals HFSA 2010 Practice Guidelines 21
Sodium Equivalents 22
Recommendations for Treatment of Stage B Heart Failure Yancy et al JACC 2013 24
Recommendations for Treatment of Stage B Heart Failure 25
Recommendations for Treatment of Stage B Heart Failure Improved M&M Start with ACEi ARB when ACEi contraindicated Routine combination ACEi/ARB contraindicated (class III) Improved Mortality (CAPRICORN) No class effect Preferred agents: Carvedilol, Metoprolol succinate, Bisoprolol Yancy et al JACC 2013 26
Treatment of Post-MI Patients with Asymptomatic LV Dysfunction 27
ACE Inhibitors in HF: From Asymptomatic LVD to Severe HF 28
The Additional Value of Beta Blockers Post-MI: CAPRICORN 29
Pharmacological Therapy for Management of Stage C HFrEF Recommendations COR LOE Diuretics Diuretics are recommended in patients with HFrEF with fluid retention I C ACE Inhibitors ACE inhibitors are recommended for all patients with HFrEF I A ARBs ARBs are recommended in patients with HFrEF who are ACE inhibitor intolerant ARBs are reasonable as alternatives to ACE inhibitor as first line therapy in HFrEF The addition of an ARB may be considered in persistently symptomatic patients with HFrEF on GDMT ***Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful *** I IIa IIb III: Harm A A A C
Pharmacological Therapy for Management of Stage C HFrEF (cont.) Recommendations COR LOE Beta Blockers Use of 1 of the 3 beta blockers proven to reduce mortality is recommended for all stable patients I A Aldosterone Antagonists Aldosterone receptor antagonists are recommended in patients with NYHA class II-IV HF who have LVEF 35% I A Aldosterone receptor antagonists are recommended in patients following an acute MI who have LVEF 40% with I B symptoms of HF or DM ***Inappropriate use of aldosterone receptor antagonists may be harmful *** III: Harm B Hydralazine and Isosorbide Dinitrate The combination of hydralazine and isosorbide dinitrate is recommended for African-Americans, with NYHA class III IV HFrEF on GDMT A combination of hydralazine and isosorbide dinitrate can be useful in patients with HFrEF who cannot be given ACE inhibitors or ARBs I IIa A B
Pharmacologic Therapy for Management of Stage C HFrEF (cont.) Recommendations COR LOE Digoxin Digoxin can be beneficial in patients with HFrEF IIa B Anticoagulation Patients with chronic HF with permanent/persistent/paroxysmal AF and an additional risk factor for cardioembolic stroke should receive chronic I A anticoagulant therapy* The selection of an anticoagulant agent should be individualized I C Chronic anticoagulation is reasonable for patients with chronic HF who have permanent/persistent/paroxysmal AF but without an additional risk factor for IIa B cardioembolic stroke* ***Anticoagulation is not recommended in patients with chronic HFrEF without AF, prior thromboembolic event, or a cardioembolic source*** III: No Benefit B Statins ***Statins are not beneficial as adjunctive therapy when prescribed solely for HF*** III: No Benefit A Omega-3 Fatty Acids Omega-3 PUFA supplementation is reasonable to use as adjunctive therapy in HFrEF or HFpEF patients IIa B
Pharmacological Therapy for Management of Stage C HFrEF (cont.) Recommendations COR LOE Other Drugs Nutritional supplements as treatment for HF are not recommended III: No in HFrEF Benefit B Hormonal therapies other than to replete deficiencies are not III: No recommended in HFrEF Benefit C Drugs known to adversely affect the clinical status of patients with HFrEF are potentially harmful and should be avoided or withdrawn III: Harm B Long-term use of an infusion of a positive inotropic drug is not recommended and may be harmful except as palliation Calcium Channel Blockers Calcium channel blocking drugs are not recommended as routine in HFrEF III: Harm III: No Benefit C A
Pharmacologic Treatment of Stage C HFrEF (Heart Failure with Reduced Ejection Fraction) 35
Pharmacologic Treatment of Stage C HFrEF (Heart Failure with Reduced Ejection Fraction) 36
ACE Inhibitors in Heart Failure: From Asymptomatic LVD to Severe HF 37
Effect of Beta Blockade on Outcome in Patients with HF and Post-MI LVD 38
COPERNICUS: EF<25%, FC III-IV (Baseline: ACEi/ARB=97%, MRA=2%, diuretics=99%, digoxin=66%) 39
ARBS in Patients Not Taking ACE Inhibitors: Val-HeFT & CHARM- Alternative 40
Aldosterone Antagonists in HF 41
Aldosterone Antagonists and Renal Function HFSA 2010 Practice Guidelines 42
Spironolactone Prescriptions After RALES Hospital Deaths After RALES 43
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Medical Therapy for Stage C HFrEF: Magnitude of Benefit Demonstrated in RCTs 46
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2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure COR LOE Recommendation I B-R ACEI or ARB or ARNI in conjunction with β blockers + MRA (where appropriate) is recommended for patients with chronic HFrEF to reduce morbidity and mortality I B-R In patients with chronic, symptomatic HFrEF NYHA class II or III who tolerate an ACEI or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality III B-R ARNI should NOT be administered concomitantly with ACEI or within 36 hours of last ACEI dose III COR C-EO ARNI should NOT be administered to patients with a history of angioedema LOE Recommendations IIa B-R Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III), stable, chronic HFrEF (LVEF 35%) who are receiving GDMT, including a β blocker at maximally tolerated dose, and who are in sinus rhythm with a heart rate 70 bpm at rest 1. Yancy CW et al. J Am Coll Cardiol. 2016;68:1476-1488.
Pathophysiology of HFrEF & Therapeutic Targets adapted from Langenickel TH, Dole WP Drug Discovery Today 201;9:131-9. 49
Effects of Neprilysin Inhibition in Heart Failure 50
PARADIGM-HF: Primary Endpoint of CV Death or Heart Failure Hospitalization 51
Sac/Val vs Enalapril on Primary Endpoint and on CV Death by Subgroups 52
PARADIGM-HF: Effect of Sac/Val vs Enalapril on the Primary Endpoint and Its Components 53
PARADIGM-HF: Adverse Events 54
ARNI harm 2016 Focused Update 55
Potential Mortality Reduction with Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure 56
New FDA-Approved Sacubitril/Valsartan 57
Ivabradine 2016 Focused Update 58
Ivabradine 59
SHIFT Study: Primary Endpoint of CV Death or Hospitalization for Worsening Heart Failure 60
SHIFT Study: Effect of Ivabradine on Outcomes 61
New FDA-Approved Ivabradine 62
Practical Points on Use of Ivabradine 63
Characteristics and Outcomes of Adult Outpatients with HF and Improved or Recovered Ejection Fraction 64
2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure Developed in Collaboration With the American Academy of Family Physicians, American College of Chest Physicians, and International Society for Heart and Lung Transplantation
HFrEF: cardiomyocyte insult neurohormonal/cardiaremodeling oxidative stress/inflammation HFpEF: Diverse pathophysiological pathways & comorbidities systemic inflammatory state Cardiac remodeling
Butler et al, Circ Heart Fail 2016
HFpEF Incidence & Prevalence HFpEF Increases More Rapidly with F>M Prevalence at Any Age Registries 2003-2012 Dhingra Curr Heart Fail Rep 2014 (EPICA study. Eur. J. Heart Fail. 2002) Studies HFpEF Cohorts Bimodal Distribution of EF in HF Dunlay S. M. et al. Circ. Heart Fail. 2012 Redfield MM et al. Nature Rev 2017
All Heart Failure Admissions 30-50% are with Preserved Ejection Fraction
Risk of Subsequent Death or HF Hospitalization is Greatest When the Time from the Last Hospitalization is Shortest
HFpEF Mortality How Do HFpEF Patient s Die? Sudden Cardiac Death Redfield MM, et al. Nautre Rev 2017
Guideline Definition of Heart Failure with Preserved Ejection Fraction? 2016 ESC HF Guidelines 2013 ACC HF Guidelines In Summary: Consensus is for using EF > 50%
Pathophysiology of HFpEF Traditional Pathophysiological Model HFpEF is a Disease of HFpEF Not a Collection of Co-Morbidities Emerging Pathophysiological Models of HFpEF Redfield MM 2016 (Franssen, et al. 2016; Paulus & Tschope 2013) Redfield MM 2016 (Franssen, et al. 2016; Paulus & Tschope 2013)
Diastolic Dysfunction Most Important Mechanism in HFpef Impaired Relaxation Normal CV Ageing Diastolic Dysfunction in HFpEF Invasive Evaluation: 47 HFpEF, 10 controls Henein et al. EHJ. 2002; 23:162-171. Diastolic Dysfunction in HFpEF Echo Evaluation: 244 HFpEF, 719 HTN, 617 controls Lam Circ 2007
Excitation Contraction Coupling Some Proposed Mechanisms of Diastolic Dysfunction in HFpEF Nitric Oxide/Natriuretic Peptide cgmp Pathway in HF Abnormalities in Spring-like Titin Protein Dysfunctional Ca Handling Increased Extracellular Fibrosis Reduced LV compliance shift PV relationship Van Heerebeek L, et a. Paulus WJ. AHA 2011 AOS 503.02, Bers & Borlaug Braunwald s Heart Dis, 11 th Ed.
Comorbidity Drive Microvascular & Coronary Endothelial Oxidative Stress & Inflammation LV, RV, LA, RA Skeletal Muscle Paulus W, JACC 2013; Stasch JP, JCI 2006 Redfield MM, Mayo CV Board Rev 2016 Kato, HAHA 2016; Mohammed, Circ HF 2016 Borlaug et al, JACC 2010
LV Systolic Function in HFpEF Myocardial Strain In Normals, HTN, HFpEF and HFrEF Subtle Systolic Dysfunction in HFpEF Kraigher-Krainer E, JACC 2013 Knappe D, Circ HF 2011 TOPCAT, A. Shah circ 2015 Borlqug JACC 2009 Decreased Systolic Reserve in HFpEF
Less Physical Activity and Higher BMI Associated with HFpEF Development
HFpEF is Caused by Complex Interplay of Multiple Impairments Ventricular diastolic and systolic reserve Heart rate reserve and rhythm Atrial dysfunction Stiffening of the ventricles and vasculature Impaired vasodilatation Pulmonary HTN Endothelial dysfunction Abnormalities in periphery, including skeletal muscle
HFpEF Treatment Guidelines European Society of Cardiology HF Guidelines 2012 No treatment has yet been shown, convincingly, to reduce morbidity and mortality in patients with HF 2016 No treatment has yet been shown, convincingly, to reduce morbidity and mortality in patients with HF-PEF
Landmark Heart Failure RCTs NO Evidence Based Therapy Effective for HFpEF
Outcomes Trials in HFpEF Solomon S ESC 2017
HFpEF Trials cgmp-pkg, sgc, NO Pathways Solomon S, ESC 2017
Some Benefit in HFpEF?
Effect of Exercise on Training on Measures of Diastolic Function Edelmann, Pieske B JACC 2011
2017 ACC Focused Update HF Guidelines Treatment of HFpEF
HFpEF Putting It All Together Assess alternative comorbidities ICH, Circ Heart Fail 2016 Redfield MM, Mayo CV Board Rev 2016 Redfield MM et al, Nature Rev 2017 Additional Objective Options: Diastolic Stress testing CPET Right & left cardiac cath EDP, CO
Thank you!!!
Top Ten Things to Know 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure 1. Heart Failure (HF) prevalence has increased from 5.7 million to 6.5 million in Americans 20 years of age and projections show prevalence will increase by 46% from 2012 to 2030 resulting in more than 8 million people 18 years of age and older with HF. 2. This update represents the second of a two-stage publication with the 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure which incorporated the use of an angiotensin receptor neprilysin inhibitor (ARNI) (valsartan/sacubitril) and a sinoatrial node modulator (ivabradine) for patients with heart failure with reduced ejection fraction (HFrEF). 90
Top Ten Things to Know 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure 3. This focused update includes the recommendations for these newer pharmacotherapies, revisions to the sections on biomarkers, heart failure with preserved ejection fraction (HFpEF), important comorbidities including sleep apnea, anemia and hypertension, and insights regarding HF prevention. 4. For patients at risk of developing heart failure, use of natriuretic peptide biomarker-based screening followed by team-based care including a cardiovascular specialist optimizing guideline-directed management and therapy (GDMT) can be useful to prevent the development of Left Ventricular (LV) dysfunction (systolic or diastolic) or new onset HF. 5. Based on observational studies, for patients hospitalized with HF, a predischarge natriuretic peptide level can be useful to establish a post-discharge prognosis. 91
Top Ten Things to Know 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure 6. For the pharmacologic treatment of Stage C HFpEF, aldosterone receptor antagonists might be considered in appropriately selected patients; however, routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality of life (QoL) in patients is not effective. 7. For patients with New York Heart Association (NYHA) class II and III HF with comorbid iron deficiency anemia, intravenous iron replacement might be reasonable to improve functional status and QoL; however, use of erythropoietin stimulating agents in patients with HF and anemia should not be used. 8. Recommendations and goals for blood pressure management have been added for patients at risk of developing HF (Stage A HF) and those with both Stage C HFrEF with hypertension and HFpEF with persistent hypertension. 92
Top Ten Things to Know 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure 9. A formal sleep assessment is reasonable for patients with NYHA class II-IV HF and suspicion of sleep disordered breathing or excessive daytime sleepiness. - Importance of diagnosing obstructive versus central sleep apnea. - Treating patients with NYHA class II-IV HFrEF and central sleep apnea with adaptive servo-ventilation (ASV) causes harm and is not recommended. 10. This focused update incorporates new data since the previous publication and emphasizes important topics including - HF prevention, - - hypertension management, and - treatment of common comorbid conditions. 93