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Introduction to
Heart Failure
Mauricio Velez, M.D.
Transplant Cardiologist
APACVS 2018
April 5-7
Miami, FL
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Disclosures
No relevant financial relationships to disclose
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Objectives and Outline
• Define heart failure and its public health significance
• Describe different classifications of HF
• Review the diagnostic evaluation of HF patients
• Discuss principles of guideline-directed management of chronic HF
• Recognize special considerations for treatment of patients hospitalized with HF
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Definition of HF
• Heart failure is a complex disease that is the result of cardiac injury that impairs the heart’s ability to eject or fill with blood
• This manifests with typical symptoms:• Fatigue and shortness of breath that limit the patient’s
ability to exercise
• Fluid retention that can cause elevated jugular venous pressure, pulmonary or peripheral edema
• Symptoms can vary if HF is acute or chronic
• HF patients can have preserved or reduced ejection fraction (EF)
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Epidemiology of HF
• Over 5 million Americans suffer from HF at present
• 650,000 new cases annually
• Over 1 million hospital visits every year
• 20% of Americans older than 40 years will develop HF
• HF incidence is about 20 per 1000 people 65-69 years old
• HF incidence rises with age and is greater than 80 per 1000 people 85 years old or older
Djousse L et al. JAMA 2009;302:394-400
Go AS et al. Circulation 2013;127:e6-245
Curtis LH et al. Arch Intern Med 2008;168:418-424
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Risk Factors for the Development of HF
Dunlay SM C et al. Am J Med 2009;122:1023-1028
Risk Factor
Prevalence among cases (%) Time From RF to
HF Onset in years,
median (25th-75th
percentile)
Overall
(n=962)
Women
(n=517)
Men
(n=445)
Coronary artery disease 29.1 21.1 38.4 4.9 (0.4-10.8)
Hypertension 66.2 72.7 58.6 15.1 (7.3-23.7)
Diabetes 18.5 16.8 20.5 9.8 (5-18.6)
Obesity 24.5 23.2 26.1 16.1 (10.1-20.4)
Ever smoker 51.2 33.7 71.6 --
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Pathophysiology of HF
Mann DL et al. Circulation 2005;111:2837-2849
MI
HTN
Arrhythmias
Valve disease
Diabetes
Toxins
Sympathetic NS
Renin-Angiotensin-
Aldosterone System
Natriuretic
Peptide System
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Natural History of HF
Allen LA et al. Circulation 2012;125:1928-1952
ONSET SUDDEN DEATH DECOMPENSATIONS PUMP FAIL
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Hospital Discharges for HF by Gender(US 1979-2009)
CMS
720k
1.1M
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HF 5-year Mortality
Roger VL et al. JAMA 2004;292:344-350
5-year mortality: 50% 5-year mortality: 46%
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Classification of HF
• Based on EF• Heart failure with reduced ejection fraction (HFrEF)
• Heart failure with preserved ejection fraction (HFpEF)• HFpEF-borderline
• HFpEF-improved
• Based on symptom severity upon assessment• NYHA class I-IV
• Based on disease progression• ACCF/AHA Stages A-D
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Classification of HF by EF
Classification EF (%) Description
1. HF with reduced EF (HFrEF) ≤40Systolic HF. Most available clinical trials
include patients with HFrEF
2. HF with preserved EF (HFpEF) ≥50 Diastolic HF. No known effective therapies
a. HFpEF-borderline 41-49New intermediate group. Appear to be
more similar to HFpEF
b. HFpEF-improved >40
Patients with reduced EF who have
improvement who may have different
characteristics to HFrEF and HFpEF
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Classification of HF by Symptom Severity
NYHA Class Description
Class INo limitation of physical activity. Ordinary activity
does not cause HF symptoms
Class IISlight limitation of physical activity. Comfortable at
rest, but ordinary activity results in HF symptoms
Class III
Marked limitation of physical activity. Comfortable
at rest, but less than ordinary activity causes HF
symptoms
Class IVUnable to carry out any physical activity without
HF symptoms or symptoms of HF at rest
The Criteria Committee of the NY Heart Association.
Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels.
9th Ed. Boston: Little & Brown; 1994
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Classification of HF by Disease Stage
ACCF/AHA Stage Description
Stage AAt high risk for HF but without structural heart
disease or HF symptoms
Stage BStructural heart disease is present but never had
HF symptoms
Stage CStructural heart disease present with HF symptoms
now or in the past
Stage DRefractory HF symptoms requiring advanced
therapies
Hunt SA et al. J Am Coll Cardiol 2009;53:e1-90
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Chronic HF Management by Disease Stage
Hunt SA et al. J Am Coll Cardiol 2005;112:e154-235
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Evaluation of HF Patients
• HF is a purely clinical diagnosis• Thorough history and physical examination should
be obtained in all patients• Assess severity of activity limitations (NYHA class)• Presence of orthopnea• HR, BP and changes in weight• Assess jugular venous pressure and extent of edema
• Laboratory testing• CBC• Serum electrolytes and glucose• BUN/creatinine• Fasting lipids• Liver function tests• Thyroid function tests
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Evaluation of HF Patients
• 12-lead electrocardiogram
• Chest X-ray
• 2D echocardiogram with Doppler• Follow up echocardiogram if:
• Significant changes in clinical status
• Suspected recovery after a clinical event
• Suspected recovery due to medical therapy
• To assess eligibility for device therapy
• Routine follow up echocardiograms are not recommended
• Cardiac MR is an alternative to echocardiography
• When CAD is suspected, non-invasive stress testing or coronary angiography is reasonable unless the patient is not a candidate for revascularization
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Biomarkers in HF
• BNP or NT-proBNP can be helpful when the cause of dyspnea is uncertain
• BNP or NT-proBNP should be checked to assess prognosis/disease severity• Entresto® can increase BNP, but not NT-proBNP
• Elevated Troponin T or I indicate poor prognosis in patients hospitalized with HF, even in the absence of acute coronary syndrome
• Soluble ST-2, galectin-3 and high-sensitivity troponin are markers of cardiac injury/fibrosis and are associated with risk of hospitalization and death
Tang WH et al. Circulation 2003;108:2964-2966
Anand IS et al. Circulation 2003;107:1278-1283
Manzano-Fernandez S et al. Am J Cardiol 2011;107:259-267
Shah RV et al. Eur J Heart Fail 2010;12:826-832
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Biomarkers in Prevention, Diagnosis and Risk-Stratification of HF
Yancy C et al. J Am Coll Cardiol 2017;70:776-803
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Principles of Chronic HF Management
• The treatment of HFrEF includes pharmacologic and non-pharmacologic components
• Pharmacologic treatment involves several medication classes which have combined effects that reduce HF mortality and morbidity• The foundation of medical therapy are ACEi/ARBs and evidence-
based beta-blockers
• Achieving guideline-directed doses of these medications is the primary goal of dose adjustment
• Non-pharmacologic treatments are just as important and include lifestyle modification/self-care behaviors and device-based therapies
• The treatment requirements change as disease progresses from Stage A to Stage D
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Management of Chronic HF Evolves by Stage
Jessup M et al. N Engl J Med 2003;348:2007-2017
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Classification of Recommendations and Levels of Evidence
Yancy C et al. J Am Coll Cardiol 2017;70:776-803
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Pathophysiology of HF
Mann DL et al. Circulation 2005;111:2837-2849
MI
HTN
Arrhythmias
Valve disease
Diabetes
Toxins
“Neurohormones”
Sympathetic NS
Renin-Angiotensin-
Aldosterone System
Natriuretic
Peptide System
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Management of Stage AChronic HF
• Aggressive management of HF risk factors
• Hypertension and abnormal lipids should be treated according to current guidelines
• Diabetes, obesity and smoking should be treated as well
• Avoid cardiotoxic exposures as possible: alcohol, certain cancer therapies, radiation therapy to the chest
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Management of Stage BChronic HF
• Patients with a history of MI, recent or remote, and a low EF, should be treated with ACEi/ARB or evidence-based beta-blockers to decrease the likelihood of HF onset
• Post-MI patients should be treated with statins to prevent HF
• In patients with LVH, hypertension should be treated according to current guidelines
• ACEi/ARB and evidence-based beta-blockers should be used in all patients with low EF to prevent HF
• An ICD is reasonable in post-MI patients without HF symptoms if they are at least 40 days post-MI, have an EF ≤30%, and are on guideline-directed medical therapy
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Management of Stage BChronic HF
🚫 Diltiazem, verapamil 🚫
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Management of Stage C Chronic HFNon-Pharmacologic Interventions
• Education on HF self-care behaviors
• Dietary sodium and fluid restriction• Reduce congestive symptoms
• Compliance with medications and follow-up• Reduce hospitalization risk
• Daily weight• Early calls to healthcare providers with volume retention
• Exercise training and cardiac rehabilitation• Improves functional capacity, quality of life and reduces mortality
Yancy C et al. J Am Coll Cardiol 2017;70:776-803
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Management of Stage C Chronic HFPharmacologic Interventions
-50
-40
-30
-20
-10
0
Enalapril(1) Carvedilol(2) Spironolactone(3) HZN/ISDN(4) Entresto®(5)
Mo
rta
lity
re
du
cti
on
(%
)
(1) N Engl J Med 1987;316:1429-1435
(2) N Engl J Med 2001;344:1651-1658
(3) N Engl J Med 1999;341:709-717
(4) N Engl J Med 2005;352:225-237
(5) N Engl J Med 2014;371:993-1004
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Management of Stage C Chronic HF
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
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Entresto® (Sacubitril-Valsartan)
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Yancy C et al. J Am Coll Cardiol 2017;70:776-803
• New drug class (ARNI)
• ARB (Valsartan) combined with neprilysin inhibitor (Sacubitril)
• Neprilysin breaks down BNP, bradykinin and other vasoactive peptides
• Use of Entresto® resulted in further 20% reduction in HF mortality and HF hospitalization compared to enalapril
• Patients who can tolerate and ACEi or ARB should be transitioned to Entresto®
• Discontinue ACEi/ARB for AT LEAST 36 HOURS before starting Entresto® to decrease risk of angioedema
• Dosed 24/26 mg (50 mg), 49/51 mg (100 mg) and 97/103 mg (200 mg) tabs
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Other Beneficial Drugs
• Digoxin• Can be used in HFrEF to reduce HF hospitalizations
• Ivabradine• Can be used in NYHA II-III HFrEF who are on GDMT, receiving a
beta-blocker at maximally-tolerated dose, who remain in sinus rhythm with heart rate ≥ 70 bpm
• Omega-3 Fatty Acids• May reduce mortality and cardiovascular hospitalizations
Digitalis Investigation Group. N Engl J Med 1997;336:525-533
Tavazzi L et al. Lancet 2008;372:1223-1230
Swedverg K et al. Lancet 2010;376:875-885
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Guideline-Directed Management & Therapy of Stage C Chronic HF
Yancy C et al. J Am Coll Cardiol 2017;71:201-230
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Guideline-Directed Management & Therapy
ACEi/ARB/ARNI
ACEi/ARB/ARNI Starting Dose Maximum DoseMean Dose
Achieved in Trial
Captopril 6.25 mg TID 50 mg TID 122.7 mg/day
Enalapril 2.5 mg BID 10 to 20 mg BID 16.6 mg/day
Lisinopril 2.5 to 5 mg Daily 20 to 40 mg Daily 32.5 to 35 mg/day
Candesartan 4 to 8 mg Daily 32 mg Daily 24 mg/day
Losartan 25 to 50 mg Daily 50 to 150 mg Daily 129 mg/day
Valsartan 20 to 40 mg BID 160 mg BID 254 mg/day
Entresto® 50 to 100 mg BID 200 mg BID 375 mg/day
N Engl J Med 1987;316:1429-1435
N Engl J Med 2001;344:1651-1658
N Engl J Med 1999;341:709-717
N Engl J Med 2005;352:225-237
N Engl J Med 2014;371:993-1004
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Guideline-Directed Management & Therapy
Beta-Blockers/HZN-ISDN/Aldo B
BB/HZN-ISDN/Aldo B Starting Dose Maximum DoseMean Dose
Achieved in Trial
Bisoprolol 1.25 mg Daily 10 mg Daily 8.6 mg/day
Carvedilol 3.125 mg BID 25 mg BID 37 mg/day
Metoprolol Succinate 12.5 to 25 mg Daily 200 mg Daily 159 mg/day
Hydralazine 25 to 50 mg TID 100 mg TID 175 mg/day
Isosorbide Dinitrate 20 to 30 mg TID 40 mg TID 90 mg/day
Spironolactone 12.5 to 25 mg BID 25 mg Daily or BID 26 mg/day
Eplerenone 25 mg Daily 50 mg Daily 42.6 mg/day
N Engl J Med 1987;316:1429-1435
N Engl J Med 2001;344:1651-1658
N Engl J Med 1999;341:709-717
N Engl J Med 2005;352:225-237
N Engl J Med 2014;371:993-1004
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Recommendations for Medical Optimization
Yancy C et al. J Am Coll Cardiol 2017;71:201-230
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ICDs and Cardiac ResynchronizationAre Important Components of GDMT
Moss AJ et al. N Engl J Med 2002;346:877-883
Abraham WT et al. N Engl J Med 2002;346:1845-1853
Moss AJ et al. N Engl J Med 1996;335:1933-1940
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Early Recognition of Stage D Heart Failure
• Repeated (≥2) hospitalizations or ED visits for HF in 1 year
• Progressive decline in renal function
• Weight loss with unknown cause (cardiac cachexia)
• Intolerance to ACEi/ARB/ARNI due to hypotension or worsening renal function
• Intolerance to beta-blockers due to hypotension or worsening HF
• Frequent SBP < 90 mmHg
• Dyspnea with bathing and dressing
• Unable to walk 1 block without dyspnea or fatigue
• High diuretic needs (i.e., > furosemide 160 mg/day)
• Progressive decline in serum sodium
• Frequent ICD shocks
Yancy C et al. J Am Coll Cardiol 2013;62:1495-1539
Referral to HF specialist for consideration
of candidacy for advanced therapies
such as LVAD or cardiac transplantation
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Acute-on-Chronic Heart Failure:The Hospitalized HF Patient
Inability to maintain simultaneous optimal volume and perfusion status
as determined by symptoms, signs or hemodynamic measures
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Acute vs. Chronic Heart Failure
Acute Heart FailureHemodynamic derangement due to
sudden ventricular dysfunction
Chronic Heart FailureProgressive decline in ventricular function
with hemodynamic adaptation
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Acute vs. Acute-on-Chronic Heart Failure
• Major end-organ
changes, minor LV
dysfunction
• Signs/symptoms
usually obvious
• Usually ischemic
• Variable end-organ
changes, major LV
dysfunction
• Signs/symptoms
often subtle,
misleading
• All etiologies
Truly Acute Acute-on-Chronic
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Precipitating Factors
• Medication/dietary non-adherence
• Acute coronary syndromes
• Arrhythmias
• Non-cardiac diseases
• COPD, renal failure, infections
• Pacemaker/ICD malfunction
• Recreational drugs and alcohol abuse
• Medication misadventures
• Disease progression
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Principles of Management ofAcute-on-Chronic Heart Failure
• Re-establish optimal volume status
• Intravenous diuretics
• Re-establish optimal end-organ perfusion
• Vasodilators or intravenous inotropes
• Reduction in beta-blocker dose
• Achieve all of the above simultaneously and as quickly as possible
• Achieve all of the above in a way that can be maintained in the outpatient setting
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Principles of Management ofAcute-on-Chronic Heart Failure
• Outpatient GDMT should be continued during the hospitalization in the absence of hypotension or other contraindications
• If the patient is not on beta-blockers, evidence-based beta-blockers can be started once volume status is normal and the patient is no longer on vasoactive drips
• When in doubt, do not hesitate to consult your heart failure cardiologist
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Beta-blocker Caveats inAcute-on-Chronic Heart Failure
• Try to continue home dose if the patient has adequate perfusion
• Decrease by 50% if the patient has signs of poor perfusion
• Discontinue completely if the patient is in cardiogenic shock or requires vasoactive drips or mechanical support
• Avoid the urge to give beta-blockers for sinus tachycardia in patients with HFrEF
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Summary
• HF is a major health problem that carries a high risk of 5-year mortality (~50%)
• About half of patients suffer from HFrEFand about half suffer from HFpEF
• NYHA class allows us to assign symptom severity -- class changes with clinical status
• ACCF/AHA stages reflect disease progression and are helpful in focusing treatment goals
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Summary
• Evaluation of HF patients relies on a thorough history and physical examination
• Key labs assess organ function and prognosis
• Echocardiography should be obtained in all patients
• Follow up echocardiograms only in specific scenarios
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Summary
• The management of chronic HF involves several drug classes aimed at neurohormones that influence HF progression
• Optimal medical therapy means that doses used in clinical trials have been achieved –medications must be uptitrated over time
• Transition symptomatic patients who can tolerate ACEi/ARB to Entresto®
• Patients with Stage D HF should be considered for LVAD/heart transplant
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Summary
• Patients with acute-on-chronic heart failure are mainly treated with volume management and, if needed, vasodilators/inotropes
• Continue GDMT uninterrupted, if possible
• Beta-blockers should be started at low dose only after volume status is normal and the patient is stable off all drips
• No beta-blockers for sinus tachycardia in HFrEF
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