2022 AHA/ACC/HFSA Guideline for the

Management of Heart Failure

Endorsed by the Heart Failure Society of America
Citation
This slide set is adapted from the 2022 AHA/ACC/HFSA Guideline for the
Management of Heart Failure. Published online ahead of print April 1, 2022,
available at: Circulation.
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063 And Journal of the
American College of Cardiology published online ahead of print April 1, 2022. J
Am Coll Cardiol. https://www.jacc.org/doi/10.1016/j.jacc.2021.12.012
 2022 Writing Committee Members*
Paul A. Heidenreich, MD, MS, FACC, FAHA, FHFSA, Chair†
Biykem Bozkurt, MD, PhD, FACC, FAHA, FHFSA, Vice Chair†
David Aguilar, MD, MSc, FAHA† Adrian F. Hernandez, MD, MHS‡
Larry A. Allen, MD, MHS, FACC, FAHA, Prateeti Khazanie, MD, MPH, FHFSA†
FHFSA† Michelle M. Kittleson, MD, PhD†
Joni J. Byun† Christopher S. Lee, PhD, RN, FAHA, FHFSA†
Monica M. Colvin, MD, MS, FAHA† Mark S. Link, MD†
Anita Deswal, MD, MPH, FACC, FAHA, Carmelo A. Milano, MD†
FHFSA‡ Lorraine C. Nnacheta, DrPH, MPH†
Shannon M. Dunlay, MD, MS, FAHA, Alexander T. Sandhu, MD, MS†
FHFSA† Lynne Warner Stevenson, MD, FACC, FAHA,
Linda R. Evers, JD† FHFSA†
James C. Fang, MD, FACC, FAHA, FHFSA† Orly Vardeny, PharmD, MS, FAHA, FHFSA║
Savitri E. Fedson, MD, MA† Amanda R. Vest, MBBS, MPH, FHFSA║
Gregg C. Fonarow, MD, FACC, FAHA, Clyde W. Yancy, MD, MSc, MACC, FAHA,
FHFSA§ FHFSA†
Salim S. Hayek, MD, FACC†
*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1
for detailed information. † ACC/AHA Representative. ‡ ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison. §Task Force Performance Measures. ║HFSA
Representative. #Former Joint Committee member; current member during the writing effort.
Top 10 Take-Home Messages
2022 Guideline for the Management of Heart Failure
 Top 10 Take Home Messages

1. Guideline-directed medical therapy (GDMT) for heart failure

(HF) with reduced ejection fraction (HFrEF) now includes 4
medication classes which include sodium-glucose
cotransporter-2 inhibitors (SGLT2i).

5
 Top 10 Take Home Messages
2. SGLT2 inhibitors have a 2a recommendation in heart failure
with mildly reduced ejection fraction (HFmrEF). Weaker
recommendations (2b) are made for ARNi, ACEi, ARB, MRA and
beta blockers in this population.

6
 Top 10 Take Home Messages

3. New recommendations for HFpEF are made for SGLT2

inhibitors (2a) , MRAs (2b) and ARNi (2b). Several prior
recommendations have been renewed including treatment of
hypertension (1), treatment of atrial fibrillation (2a), use of ARBs
(2b) avoidance of routine use of nitrates or phosphodiesterase-5
inhibitors (3-no Benefit).

7
 Top 10 Take Home Messages

4. Improved LVEF is used to refer to those patients with a

previous HFrEF who now have an LVEF > 40%. These patients
should continue their HFrEF treatment.

8
 Top 10 Take Home Messages

5. Value statements were created for select recommendations

where high-quality cost-effectiveness studies of the intervention
have been published.

9
 Top 10 Take Home Messages

6. Amyloid heart disease has new recommendations for

treatment including screening for serum and urine monoclonal
light chains, bone scintigraphy, genetic sequencing, tetramer
stabilizer therapy, and anticoagulation.

10
 Top 10 Take Home Messages

7. Evidence supporting increased filling pressures is important

for the diagnosis of HF if the LVEF is >40%. Evidence for increased
filling pressures can be obtained from non-invasive (e.g.,
natriuretic peptide, diastolic function on imaging) or invasive
testing (e.g., hemodynamic measurement).

11
 Top 10 Take Home Messages

8. Patients with advanced HF who wish to prolong survival

should be referred to a team specializing in HF. A heart failure
specialty team reviews HF management, assesses suitability for
advanced HF therapies and uses palliative care including
palliative inotropes where consistent with the patient’s goals of
care.

12
 Top 10 Take Home Messages
9. Primary prevention is important for those at risk for HF (Stage
A) or pre-HF (Stage B). Stages of HF were revised to emphasize
the new terminologies of “at risk” for HF for Stage A and Pre-HF
for Stage B.

13
 Top 10 Take Home Messages

10. Recommendations are provided for select patients with HF

and iron deficiency, anemia, hypertension, sleep disorders, type
2 diabetes, atrial fibrillation, coronary artery disease and
malignancy.

14
 CLASS (STRENGTH) OF RECOMMENDATION LEVEL (QUALITY) OF EVIDENCE‡
CLASS 1 (STRONG) Benefit >>> LEVEL A
Risk
• High-quality evidence‡ from more than 1 RCT
Suggested phrases for writing recommendations: • Meta-analyses of high-quality RCTs
• Is recommended • One or more RCTs corroborated by high-quality registry studies
• Is indicated/useful/effective/beneficial

Table 2. Applying
• Should be performed/administered/other LEVEL B-R (Randomized)
• Comparative-Effectiveness Phrases†:
− Treatment/strategy A is recommended/indicated in preference to • Moderate-quality evidence‡ from 1 or more RCTs

American College of treatment B • Meta-analyses of moderate-quality RCTs

− Treatment A should be chosen over treatment B
LEVEL B-NR (Nonrandomized)

Cardiology/American CLASS 2a (MODERATE)

Risk
Benefit >> • Moderate-quality evidence‡ from 1 or more well-designed, well-executed
nonrandomized studies, observational studies, or registry studies

Heart Association Suggested phrases for writing recommendations:

• Is reasonable
• Meta-analyses of such studies

Class of
• Can be useful/effective/beneficial
• Comparative-Effectiveness Phrases†:
LEVEL C-LD (Limited Data)
− Treatment/strategy A is probably recommended/indicated in • Randomized or nonrandomized observational or registry studies with

Recommendation
preference to treatment B limitations of design or execution
− It is reasonable to choose treatment A over treatment B • Meta-analyses of such studies
• Physiological or mechanistic studies in human subjects

and Level of Evidence CL ASS 2b (Weak)

Risk
Benefit ≥
LEVEL C-EO (Expert Opinion)

to Clinical Strategies, Suggested phrases for writing recommendations:

• May/might be reasonable
• May/might be considered
• Consensus of expert opinion based on clinical experience.

Interventions, • Usefulness/effectiveness is unknown/unclear/uncertain or not well-

established
•COR and LOE are determined independently (any COR may be paired with any LOE).
•A recommendation with LOE C does not imply that the recommendation is weak. Many

Treatments, or
important clinical questions addressed in guidelines do not lend themselves to clinical
CLASS 3: No Benefit (MODERATE) Benefit = trials. Although RCTs are unavailable, there may be a very clear clinical consensus that a
particular test or therapy is useful or effective.
Risk

Diagnostic Testing in
•*The outcome or result of the intervention should be specified (an improved clinical
Suggested phrases for writing recommendations: outcome or increased diagnostic accuracy or incremental prognostic information).
• Is not recommended
• †For comparative-effectiveness recommendation (COR 1 and 2a; LOE A and B only),

Patient Care
• Is not indicated/useful/effective/beneficial studies that support the use of comparator verbs should involve direct comparisons of the
• Should not be performed/administered/other treatments or strategies being evaluated.
•‡The method of assessing quality is evolving, including the application of standardized,

(Updated May 2019)*

CLASS 3: Harm (STRONG) Risk > widely-used, and preferably validated evidence grading tools; and for systematic reviews,
Benefit the incorporation of an Evidence Review Committee.
•COR indicates Class of Recommendation; EO, expert opinion; LD, limited data; LOE, Level
Suggested phrases for writing recommendations: of Evidence; NR, nonrandomized; R, randomized; and RCT, randomized controlled trial.
• Potentially harmful
• Causes harm
• Associated with excess morbidity/mortality
• Should not be performed/administered/other

15
Definition of HF

16
 Table 3. Stages of HF

Stages Definition and Criteria

Stage A: At Risk for HF At risk for HF but without symptoms, structural heart
disease, or cardiac biomarkers of stretch or injury (e.g.,
patients with hypertension, atherosclerotic CVD, diabetes,
metabolic syndrome and obesity, exposure to cardiotoxic
agents, genetic variant for cardiomyopathy, or positive
family history of cardiomyopathy).

17
 Table 3. Stages of HF (con’t.)

Stage B: Pre-HF No symptoms or signs of HF and evidence of 1 of the following:

Structural heart disease*
• Reduced left or right ventricular systolic function
o Reduced ejection fraction, reduced strain
• Ventricular hypertrophy
• Chamber enlargement
• Wall motion abnormalities
• Valvular heart disease
Evidence for increased filling pressures*
• By invasive hemodynamic measurements
• By noninvasive imaging suggesting elevated filling pressures (e.g.,
Doppler echocardiography)
Patients with risk factors and
• Increased levels of BNPs* or
• Persistently elevated cardiac troponin
in the absence of competing diagnoses resulting in such biomarker
elevations such as acute coronary syndrome, CKD, pulmonary
embolus, or myopericarditis

18
 Table 3. Stages of HF (con’t.)

Structural heart disease with current or previous symptoms of HF.

Stage C: Symptomatic HF

Marked HF symptoms that interfere with daily life and with

Stage D: Advanced HF recurrent hospitalizations despite attempts to optimize GDMT.

BNP indicates B-type natriuretic peptide; CKD, chronic kidney

disease; GDMT, guideline-directed medical therapy; HF,
heart failure; LV, left ventricular; and RV, right ventricular.

19
Figure 1.
ACC/AHA
Stages of
HF

The ACC/AHA
stages of HF are
shown.
ACC indicates
American College of
Cardiology; AHA,
American Heart
Association; CVD,
cardiovascular
disease; GDMT,
guideline-directed
medical therapy;
and HF, heart
failure.

20
 Figure 2. Trajectory of Class C HF

The trajectory of stage C

HF is displayed. Patients
whose symptoms and
signs of HF are resolved
are still stage C and
should be treated
accordingly. If all HF
sy mptoms, signs, and
structural abnormalities
resolve, the patient is
considered to have HF in
remission.
*Full resolution of
structural and functional
cardiac abnormalities is
uncommon.
HF indicates heart
failure; and LV, left
ventricular.

21
 Table 4. Classification of HF by LVEF

Type of HF According to LVEF Criteria

• LVEF ≤40%
HFrEF (HF with reduced EF)
• Previous LVEF ≤40% and a follow-up measurement of LVEF >40%
HFimpEF (HF with improved

EF)
• LVEF 41%–49%
HFmrEF (HF with mildly • Evidence of spontaneous or provokable increased LV filling pressures (e.g.,
elevated natriuretic peptide, noninvasive and invasive hemodynamic
reduced EF) measurement)
• LVEF ≥50%
HFpEF (HF with preserved EF) • Evidence of spontaneous or provokable increased LV filling pressures (e.g.,
elevated natriuretic peptide, noninvasive and invasive hemodynamic
measurement)
HF indicates heart failure; LV, left ventricular; and LVEF, left ventricular ejection fraction.

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Figure 3. Classification and Trajectories of HF Based on LVEF

23
Figure 4.
Diagnostic
Algorithm for HF
and EF-Based
Classification
The algorithm for a diagnosis of
HF and EF-based classification is
shown.
BNP indicates B-type natriuretic
peptide; ECG,
electrocardiogram; EF, ejection
fraction; HF, heart failure;
HFmrEF, heart failure with mildly
reduced ejection fraction;
HFpEF, heart failure with
preserved ejection fraction;
HFrEF, heart failure with reduced
ejection fraction; LVEF, left
ventricular ejection fraction; LV,
left ventricular; NP, natriuretic
peptides; and NT-proBNP, N-
terminal pro-B type natriuretic
peptide.

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Initial and Serial Evaluation

25
Clinical Assessment: History and Physical Examination
Recommendations for Clinical Assessment: History and Physical Examination

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HF, vital signs and evidence of clinical congestion should be

1 B-NR assessed at each encounter to guide overall management, including adjustment of

diuretics and other medications.

2. In patients with symptomatic HF, clinical factors indicating the presence of

1 B-NR advanced HF should be sought via the history and physical examination.

26
 Clinical Assessment: History and Physical
Examination (con’t.)
3. In patients with cardiomyopathy, a 3-generation family history should be obtained or

1 B-NR updated when assessing the cause of the cardiomyopathy to identify possible

inherited disease.
4. In patients presenting with HF, a thorough history and physical examination should

1 B-NR direct diagnostic strategies to uncover specific causes that may warrant disease-

specific management.

5. In patients presenting with HF, a thorough history and physical examination should

be obtained and performed to identify cardiac and noncardiac disorders, lifestyle

1 C-EO
and behavioral factors, and social determinants of health that might cause or

accelerate the development or progression of HF.

27
 Table 5. Other Potential Nonischemic Causes of HF

Cause Reference
Chemotherapy and other cardiotoxic medications
(23-25)
Rheumatologic or autoimmune
(26)
Endocrine or metabolic (thyroid, acromegaly, pheochromocytoma, diabetes, obesity)
(27-31)
Familial cardiomyopathy or inherited and genetic heart disease
(32)
Heart rhythm–related (e.g., tachycardia-mediated, PVCs, RV pacing)
(33)
Hypertension
(34)
Infiltrative cardiac disease (e.g., amyloid, sarcoid, hemochromatosis)
(21, 35, 36)
Myocarditis (infectious, toxin or medication, immunological, hypersensitivity)
(37, 38)
Peripartum cardiomyopathy
HF indicates heart
(39)
failure; PVC, premature Stress cardiomyopathy (Takotsubo)
ventricular contraction;
(40, 41)
Substance abuse (e.g., alcohol, cocaine, methamphetamine)
and RV, right ventricular. (42-44)

28
 Initial Laboratory and
Electrocardiographic Testing
Recommendations for Initial Laboratory and Electrocardiographic Testing

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. For patients presenting with HF, the specific cause of HF should be explored using
1 B-NR
additional laboratory testing for appropriate management.

2. For patients who are diagnosed with HF, laboratory evaluation should include

complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum
1 C-EO
creatinine, glucose, lipid profile, liver function tests, iron studies, and thyroid-

stimulating hormone to optimize management.

3. For all patients presenting with HF, a 12-lead ECG should be performed at the initial
1 C-EO
encounter to optimize management.

29
 Use of Biomarkers for Prevention, Initial
Diagnosis, and Risk Stratification

4.2. Recommendations for Use of Biomarkers for Prevention, Initial Diagnosis, and Risk Stratification

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients presenting with dyspnea, measurement of B-type natriuretic peptide

1 A (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) is

useful to support a diagnosis or exclusion of HF.

2. In patients with chronic HF, measurements of BNP or NT-proBNP levels are

1 A
recommended for risk stratification.

30
 Use of Biomarkers for Prevention, Initial
Diagnosis, and Risk Stratification (con’t.)

3. In patients hospitalized for HF, measurement of BNP or NT-proBNP levels at

1 A
admission is recommended to establish prognosis.

4. In patients at risk of developing HF, BNP or NT-proBNP–based screening followed by

team-based care, including a cardiovascular specialist, can be useful to prevent the

2a B-R
development of LV dysfunction or new-onset HF.

5. In patients hospitalized for HF, a predischarge BNP or NT-proBNP level can be useful
2a B-NR
to inform the trajectory of the patient and establish a postdischarge prognosis

31
Table 6. Selected Potential Causes of Elevated
Natriuretic Peptide Levels

Cardiac
HF, including RV HF syndromes
ACS
Heart muscle disease, including LVH
VHD
Pericardial disease
AF
Myocarditis
Cardiac surgery
Cardioversion
Toxic-metabolic myocardial insults,
including cancer chemotherapy

32
 Table 6. Selected Potential Causes of Elevated
Natriuretic Peptide Levels (50-53) (con’t.)
Noncardiac
Advancing age
Anemia
Renal failure
Pulmonary: Obstructive sleep apnea, severe
pneumonia
Pulmonary embolism, pulmonary arterial
hypertension
Critical illness
Bacterial sepsis
ACS indicates acute coronary Severe burns
sy ndromes; AF, atrial fibrillation; HF,
heart failure; LVH, left ventricular
hy pertrophy; RV, right ventricular; and
V HD, valvular heart disease.

33
 Genetic Evaluation and Testing

Recommendations for Genetic Evaluation and Testing

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In first-degree relatives of selected patients with genetic or inherited cardiomyopathies,

1 B-NR genetic screening and counseling are recommended to detect cardiac disease and prompt

consideration of treatments to decrease HF progression and sudden death.

2. In select patients with nonischemic cardiomyopathy, referral for genetic counseling and

2a B-NR testing is reasonable to identify conditions that could guide treatment for patients and family

members.

34
 Table 7. Examples of Factors Implicating Possible
Genetic Cardiomyopathy

Phenotypic Category Patient or Family Member Phenotypic Finding* Ask Specifically About Family Members*

With
Cardiac morphology Marked LV hypertrophy Any mention of cardiomyopathy, enlarged
LV noncompaction or weak heart, HF.
Right ventricular thinning or fatty replacement on

imaging or biopsy
Document even if attributed to other causes,

such as alcohol or peripartum

cardiomyopathy
Findings on 12-lead ECG Abnormal high or low voltage or conduction, and Long QT or Brugada syndrome

repolarization, altered RV forces

35
 Table 7. Examples of Factors Implicating Possible
Genetic Cardiomyopathy (con’t.)
ICD
Dysrhythmias Frequent NSVT or very frequent PVCs Recurrent syncope
Sustained ventricular tachycardia or fibrillation Sudden death attributed to “massive
heart attack” without known CAD

Unexplained fatal event such as

drowning or single-vehicle crash

Early onset AF “Lone” AF before age 65 years

Early onset conduction disease Pacemaker before age 65 years
Any known skeletal muscle disease,
Extracardiac features • Skeletal myopathy including mention of Duchenne and
AF indicates atrial
• Neuropathy Becker’s, Emory-Dreifuss limb-girdle
fibrillation; CAD, • Cutaneous stigmata dystrophy
coronary artery
disease; LV, left
• Other possible manifestations of systemic
ventricular; NSVT, syndromes Systemic syndromes:
nonsustained
ventricular
• Dysmorphic features
tachycardia; PVC, • Mental retardation
premature
ventricular
• Congenital deafness
contraction; and • Neurofibromatosis
RV , right
ventricular.
• Renal failure with neuropathy

36
 Evaluation With Cardiac Imaging
Recommendations for Evaluation With Cardiac Imaging

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with suspected or new-onset HF, or those presenting with acute

decompensated HF, a chest x-ray should be performed to assess heart size and
1 C-LD
pulmonary congestion and to detect alternative cardiac, pulmonary, and other

diseases that may cause or contribute to the patient’s symptoms.

2. In patients with suspected or newly diagnosed HF, transthoracic

1 C-LD echocardiography (TTE) should be performed during initial evaluation to

assess cardiac structure and function.

37
 Evaluation With Cardiac Imaging (con’t.)

3. In patients with HF who have had a significant clinical change, or who have received

GDMT and are being considered for invasive procedures or device therapy, repeat
1 C-LD
measurement of EF, degree of structural remodeling, and valvular function are useful

to inform therapeutic interventions.

4. In patients for whom echocardiography is inadequate, alternative imaging (e.g.,

1 C-LD cardiac magnetic resonance [CMR], cardiac computed tomography [CT], radionuclide

imaging) is recommended for assessment of LVEF.

5. In patients with HF or cardiomyopathy, CMR can be useful for diagnosis or

2a B-NR
management.

38
 Evaluation With Cardiac Imaging (con’t.)
6. In patients with HF, an evaluation for possible ischemic heart disease can be useful to identify

2a B-NR the cause and guide management.

7. In patients with HF and CAD who are candidates for coronary revascularization, noninvasive

stress imaging (stress echocardiography, single-photon emission CT [SPECT], CMR, or

2b B-NR
positron emission tomography [PET]) may be considered for detection of myocardial ischemia

to help guide coronary revascularization.

8. In patients with HF in the absence of: 1) clinical status change, 2) treatment interventions that

might have had a significant effect on cardiac function, or 3) candidacy for invasive
3: No Benefit C-EO
procedures or device therapy, routine repeat assessment of LV function is not indicated.

39
 Invasive Evaluation

Recommendations for Invasive Evaluation

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HF, endomyocardial biopsy may be useful when a specific

2a B-NR diagnosis is suspected that would influence therapy.

40
 Invasive Evaluation (con’t.)

2. In selected patients with HF with persistent or worsening symptoms,

signs, diagnostic parameters, and in whom hemodynamics are

2a C-EO
uncertain, invasive hemodynamic monitoring can be useful to guide

management.

3: No 3. In patients with HF, routine use of invasive hemodynamic monitoring is

B-R
Benefit not recommended.

4. For patients undergoing routine evaluation of HF, endomyocardial

3: Harm C-LD biopsy should not be performed because of the risk of complications.

41
 Wearables and Remote Monitoring (Including
Telemonitoring and Device Monitoring)
Recommendation for Wearables and Remote Monitoring (Including Telemonitoring and Device Monitoring)

Referenced studies that support the recommendation are summarized in the Online Data Supplements.
COR LOE Recommendation
1. In selected adult patients with NYHA class III HF and history of a HF hospitalization in the past

year or elevated natriuretic peptide levels, on maximally tolerated stable doses of GDMT with
2b B-R
optimal device therapy, the usefulness of wireless monitoring of PA pressure by an implanted

hemodynamic monitor to reduce the risk of subsequent HF hospitalizations is uncertain.

2. In patients with NYHA class III HF with a HF hospitalization within the previous year, wireless
Value Statement:
monitoring of the PA pressure by an implanted hemodynamic monitor provides uncertain value .
Uncertain Value (B-NR)

42
 Exercise and Functional Capacity Testing
Recommendations for Exercise and Functional Capacity Testing

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In patients with HF, assessment and documentation of NYHA functional classification are
1 C-LD
recommended to determine eligibility for treatments.
2. In selected ambulatory patients with HF, cardiopulmonary exercise testing (CPET) is

1 C-LD recommended to determine appropriateness of advanced treatments (e.g., LVAD, heart

transplant).
3. In ambulatory patients with HF, performing a CPET or 6- minute walk test is reasonable to
2a C-LD
assess functional capacity.
4. In ambulatory patients with unexplained dyspnea, CPET is reasonable to evaluate the cause
2a C-LD
of dyspnea.

43
 Initial and Serial Evaluation: Clinical
Assessment: HF Risk Scoring

Recommendation for Initial and Serial Evaluation: Clinical Assessment: HF Risk Scoring

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In ambulatory or hospitalized patients with HF, validated multivariable risk

2a B-NR scores can be useful to estimate subsequent risk of mortality.

44
Table 8. Selected Multivariable Risk Scores to
Predict Outcome in HF
Risk Score Year Published

Chronic HF

All Patients With Chronic HF

Seattle Heart Failure Model 2006

https://depts.washington.edu/shfm/?width=1440&h
eight=900
Heart Failure Survival Score 1997
MAGGIC 2013
http://www.heartfailurerisk.org/
CHARM Risk Score 2006
CORONA Risk Score 2009
Specific to Chronic HFrEF

PARADIGM-HF 2020
HF-ACTION 2012
GUIDE-IT 2019

45
 Table 8. Selected Multivariable Risk Scores to
Predict Outcome in HF (con’t.)
Specific to Chronic HFpEF
I-PRESERVE Score (9) 2011

ADHERE indicates Acute

Decompensated Heart Failure
TOPCAT (10) 2020
National Registry; AHA, indicates Acutely Decompensated HF
American Heart Association; ARIC,
Atherosclerosis Risk in Communities; ADHERE Classification and (11) 2005
CHARM, Candesartan in Heart failure- Regression Tree (CART) Model
Assessment of Reduction in Mortality
and morbidity; CORONA, Controlled
Rosuvastatin Multinational Trial in
Heart Failure; EFFECT, Enhanced
Feedback for Effective Cardiac AHA Get With The Guidelines (12) 2010, 2021
Treatment; ESCAPE, Evaluation Study Score https://www.mdcalc.com/gwtg-
of Congestive Heart Failure and
Pulmonary Artery Catheterization heart-failure-risk-score (17)
Effectiveness; GUIDE-ID, Guiding
Evidence-Based Therapy Using
Biomarker Intensified Treatment; HF,
heart failure; HFpEF, heart failure with
preserved ejection fraction; HF-
ACTION, Heart Failure: A Controlled
EFFECT Risk Score (13) 2003, 2016
Trial Investigating Outcomes of http://www.ccort.ca/Research/CHF
Exercise Training MAGGIC Meta-
analysis Global Group in Chronic
RiskModel.aspx (18)
Heart Failure; I-PRESERVE, Irbesartan
in Heart Failure with Preserved Ejection
Fraction Study; PCP-HF, Pooled Cohort
Equations to Prevent HF; TOPCAT, ESCAPE Risk Model and (14) 2010
Treatment of Preserved Cardiac
Function Heart Failure with an
Discharge Score
Aldosterone Antagonist trial.

46
Stage A (Patients at Risk for HF)

47
 Patients at Risk for HF (Stage A: Primary
Prevention)
Recommendations for Patients at Risk for HF (Stage A: Primary Prevention)

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with hypertension, blood pressure should be controlled in accordance with

1 A
GDMT for hypertension to prevent symptomatic HF.

2. In patients with type 2 diabetes and either established CVD or at high cardiovascular
1 A
risk, SGLT2i should be used to prevent hospitalizations for HF.

48
 Patients at Risk for HF (Stage A: Primary
Prevention) (con’t.)
3. In the general population, healthy lifestyle habits such as regular physical activity,

1 B-NR maintaining normal weight, healthy dietary patterns, and avoiding smoking are

helpful to reduce future risk of HF.

4. For patients at risk of developing HF, natriuretic peptide biomarker–based

screening followed by team-based care, including a cardiovascular specialist

2a B-R
optimizing GDMT, can be useful to prevent the development of LV dysfunction

(systolic or diastolic) or new-onset HF.

5. In the general population, validated multivariable risk scores can be useful to
2a B-NR
estimate subsequent risk of incident HF.

49
 Figure 5.
Recommendations
(Class 1 and 2a) for
Patients at Risk of
HF (Stage A) and
Those With Pre-HF
(Stage B)
Colors correspond to COR in Table 2.

Class 1 and Class 2a recommendations for

patients at risk for HF (stage A) and those with
pre-HF (stage B) are shown. Management
strategies implemented in patients at risk for
HF (stage A) should be continued though
stage B.
ACEi indicates angiotensin-converting enzyme
inhibitor; ARB, angiotensin receptor blocker;
BP, blood pressure; CVD, cardiovascular
disease; HF, heart failure; ICD, implantable
cardioverter-defibrillator; LVEF, left ventricular
ejection fraction; MI, myocardial infarction;
and SGLT2i, sodium glucose cotransporter 2
inhibitor.

50
Table 9. Selected Multivariable Risk Scores to Predict
Development of Incident HF

Risk Score Year Published

1999
Framingham Heart Failure Risk Score
2008
Health ABC Heart Failure Score
2012
ARIC Risk Score
2019
PCP-HF

HF indicates heart failure; and PCP-HF, Pooled Cohort Equations to Prevent HF.

51
Stage B (Patients With Pre-HF)

52
 Management of Stage B: Preventing the
Syndrome of Clinical HF in Patients With Pre-HF
Recommendations for Management of Stage B: Preventing the Syndrome of Clinical HF in Patients With Pre-HF

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In patients with LVEF ≤40%, ACEi should be used to prevent symptomatic HF and reduce
1 A
mortality.
2. In patients with a recent or remote history of MI or ACS, statins should be used to prevent
1 A
symptomatic HF and adverse cardiovascular events.
3. In patients with a recent or remote history of MI or acute coronary syndrome (ACS) and LVEF
1 B-R
≤40%, evidence-based beta blockers should be used to reduce mortality.

53
 Management of Stage B: Preventing the
Syndrome of Clinical HF in Patients With
Pre-HF (con’t.)
4. In patients with a recent or remote history of MI or ACS, statins should be used to prevent
1 B-R
symptomatic HF and adverse cardiovascular events.
5. In patients who are at least 40 days post-MI with LVEF ≤30% and NYHA class I symptoms while

1 B-R receiving GDMT and have reasonable expectation of meaningful survival for >1 year, an ICD is

recommended for primary prevention of sudden cardiac death (SCD) to reduce total mortality.

1 C-LD 6. In patients with LVEF ≤40%, beta blockers should be used to prevent symptomatic HF.

7. In patients with LVEF <50%, thiazolidinediones should not be used because they increase the risk of
3: Harm B-R
HF, including hospitalizations.
8. In patients with LVEF <50%, nondihydropyridine calcium channel blockers with negative inotropic
3: Harm C-LD
effects may be harmful.

54
 Table 10. Other ACC/AHA Clinical Practice Guidelines
Addressing Patients With Stage B HF

Consideration Reference
Patients with an acute MI who have not developed HF symptoms 2013 ACCF/AHA Guideline for the Management of ST-
treated in accordance with GDMT Elevation Myocardial Infarction

2014 AHA/ACC Guideline for the Management of Patients With

Non–ST-Elevation Acute Coronary Syndromes
Coronary revascularization for patients without symptoms of HF 2015 ACC/AHA/SCAI Focused Update on Primary
in accordance with GDMT Percutaneous Coronary Intervention for Patients With ST-
Elevation Myocardial Infarction: An Update of the 2011
ACCF/AHA/SCAI Guideline for Percutaneous Coronary
Intervention and the 2013 ACCF/AHA Guideline for the
Management of ST-Elevation Myocardial Infarction (This
guideline has been replaced by Lawton, 2021.)

2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the

Guideline for the Diagnosis and Management of Patients With
Stable Ischemic Heart Disease

2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft

Surgery (This guideline has been replaced by Lawton, 2021.)

55
 Table 10. Other ACC/AHA Clinical Practice Guidelines
Addressing Patients With Stage B HF (con’t.)
Valve replacement or repair for patients with 2020 ACC/AHA Guideline for the Management of

hemodynamically significant valvular stenosis or Patients With Valvular Heart Disease

regurgitation and no symptoms of HF in accordance

AATS indicates American with GDMT

Association for Thoracic
Surgery; ACC, American
College of Cardiology;
ACCF, American College
of Cardiology
Foundation; AHA,
American Heart
Association; GDMT,
guideline-directed
medical therapy; HF,
heart failure; MI,
my ocardial infarction; Patients with congenital heart disease that may increase 2018 AHA/ACC Guideline for the Management of
PCNA, Preventive
Cardiovascular Nurses
Association; SCAI, the risk for the development of HF Adults With Congenital Heart Disease
Society for
Cardiovascular
Angiography and
Interventions; and STS,
The Society of Thoracic
Surgeons.

56
Stage “C” HF

57
 Nonpharmacological Interventions: Self-
Care Support in HF
Recommendations for Nonpharmacological Interventions: Self-Care Support in HF

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. Patients with HF should receive care from multidisciplinary teams to

facilitate the implementation of GDMT, address potential barriers to

1 A
self-care, reduce the risk of subsequent rehospitalization for HF, and

improve survival.

58
 Nonpharmacological Interventions: Self-
Care Support in HF (con’t.)

2. Patients with HF should receive specific education and support to facilitate

1 B-R
HF self-care in a multidisciplinary manner.

3. In patients with HF, vaccinating against respiratory illnesses is reasonable to

2a B-NR
reduce mortality.

4. In adults with HF, screening for depression, social isolation, frailty, and low

2a B-NR health literacy as risk factors for poor self-care is reasonable to improve

management.

59
 Table 11. Potential Barriers to Effective HF Self-Care
and Example Interventions

Potential Barrier Example Screening Tools Example Interventions

Medical Barriers
Cognitive impairment Mini-Cog Home health aide

Mini-Mental State Examination (MMSE) Home meal deliveries

Montreal Cognitive Assessment (MoCA) Adult day care

Geriatric psychiatry referral

Memory care support groups

Depression Hamilton Depression Rating Scale (HAM-D) Psychotherapy

Beck Depression Inventory-II (BDI-II) Selective serotonin reuptake inhibitors

Patient Health Questionnaire-9 (PHQ-9) Nurse-led support

60
 Table 11. Potential Barriers to Effective HF Self-Care
and Example Interventions (con’t.)

Substance use disorders Tobacco, Alcohol, Prescription medication, and Referral to social work services and

other Substance use (TAPS) community support partners

Referral for addiction psychiatry consultation

Frailty Fried frailty phenotype Cardiac rehabilitation

Registered dietitian nutritionist evaluation for

malnutrition
Social Barriers
Financial burden of HF treatments COmprehensive Score for financial Toxicity– PharmD referral to review prescription

Functional Assessment of Chronic Illness assistance eligibilities

Therapy (COST-FACIT)

61
 Table 11. Potential Barriers to Effective HF Self-Care
and Example Interventions (con’t.)

Food insecurity Hunger Vital Sign, 2 items Determine eligibility for the Supplemental

U.S. Household Food Security Survey Nutrition Assistance Program (SNAP)

Module, 6 items Connect patients with community partners

such as food pantries/food banks

Home meal deliveries

Registered dietitian nutritionist evaluation for

potential malnutrition
Homelessness or housing insecurity Homelessness Screening Clinical Reminder Referral to local housing services

(HSCR) Connect patients with community housing

partners

62
 Table 11. Potential Barriers to Effective HF Self-Care
and Example Interventions (con’t.)

Intimate partner violence or elder Humiliation, Afraid, Rape, Kick (HARK) Referral to social work services and

abuse questionnaire community support partners

Partner Violence Screen (PVS)

Woman Abuse Screening Tool (WAST)

Limited English proficiency or other Routinely inquire in which language the patient Access to interpreter services covering a wide

language barriers is most comfortable conversing range of languages, ideally in person or,

alternatively, via video platform

Printed educational materials in a range of

appropriate languages

63
 Table 11. Potential Barriers to Effective HF Self-Care
and Example Interventions (con’t.)

Low health literacy Short Assessment of Health Literacy (SAHL) Agency for Healthcare Research and Quality

Rapid Estimate of Adult Literacy in Medicine– (AHRQ) Health Literacy Universal

Short Form (REALM-SF) Precautions Toolkit

Brief Health Literacy Screen (BHLS), 3 items Written education tools provided at sixth

grade reading level or below

Graphic educational documents

Social isolation or low social support Patient-Reported Outcomes Measurement Determine eligibility for home care services

Information System (PROMIS) Social Isolation Support group referral

Short Form

64
 Table 11. Potential Barriers to Effective HF Self-Care
and Example Interventions (con’t.)

Transport limitations No validated tools currently available. Referral to social work services

Determine eligibility for insurance or state-

based transportation, or reduced-cost public

transportation

Maximize opportunities for telehealth visits

and remote monitoring

HF indicates heart failure.

65
 Dietary Sodium Restriction

Recommendation for Dietary Sodium Restriction

COR LOE Recommendation

1. For patients with stage C HF, avoiding excessive sodium intake is reasonable
2a C-LD
to reduce congestive symptoms.

66
Management of Stage C HF: Activity, Exercise
Prescription, and Cardiac Rehabilitation
Recommendations for Management of Stage C HF: Activity, Exercise Prescription, and Cardiac

Rehabilitation

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations

1. For patients with HF who are able to participate, exercise training (or regular

1 A physical activity) is recommended to improve functional status, exercise

performance, and QOL.

2. In patients with HF, a cardiac rehabilitation program can be useful to improve

2a B-NR functional capacity, exercise tolerance, and health-related QOL.

67
 Diuretics and Decongestion Strategies in
Patients With HF
Recommendations for Diuretics and Decongestion Strategies in Patients With HF

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HF who have fluid retention, diuretics are recommended to relieve
1 B-NR
congestion, improve symptoms, and prevent worsening HF.

2. For patients with HF and congestive symptoms, addition of a thiazide (e.g., metolazone)

1 B-NR to treatment with a loop diuretic should be reserved for patients who do not respond to

moderate- or high-dose loop diuretics to minimize electrolyte abnormalities.

68
Table 12. Commonly Used Oral Diuretics in
Treatment of Congestion for Chronic HF

Drug Initial Daily Maximum Duration of

Dose Total Daily Action

Dose
Loop diuretics
Bumetanide 0.5–1.0 mg 10 mg 4–6 h

once or twice
Furosemide 20–40 mg 600 mg 6–8 h

once or twice
Torsemide 10–20 mg 200 mg 12–16 h

once

69
 Table 12. Commonly Used Oral Diuretics in
Treatment of Congestion for Chronic HF (con’t.)

Thiazide diuretics
Chlorthiazide 250–500 mg 1000 mg 6–12 h

once or twice
Chlorthalidone 12.5–25 mg 100 mg 24–72 h

once
Hydrochloro- 25 mg once or 200 mg 6–12 h

thiazide twice
Indapamide 2.5 mg once 5 mg 36 h
Metolazone 2.5 mg once 20 mg 12–24 h
HF indicates heart failure.

70
Renin-Angiotensin System Inhibition With ACEi
or ARB or ARNi
Recommendations for Renin-Angiotensin System Inhibition With ACEi or ARB or ARNi

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HFrEF and NYHA class II to III symptoms, the use of ARNi is
1 A
recommended to reduce morbidity and mortality.

2. In patients with previous or current symptoms of chronic HFrEF, the use of

1 A ACEi is beneficial to reduce morbidity and mortality when the use of ARNi is

not feasible.

71
 Renin-Angiotensin System Inhibition With ACEi
or ARB or ARNi (con’t.)
3. In patients with previous or current symptoms of chronic HFrEF who are intolerant

to ACEi because of cough or angioedema and when the use of ARNi is not feasible,
1 A
the use of ARB is recommended to reduce morbidity and mortality.

4. In patients with previous or current symptoms of chronic HFrEF, in whom ARNi is

Value Statement: High
not feasible, treatment with an ACEi or ARB provides high economic value.
Value (A)

5. In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an

1 B-R ACEi or ARB, replacement by an ARNi is recommended to further reduce

morbidity and mortality.

72
 Renin-Angiotensin System Inhibition With ACEi
or ARB or ARNi (con’t.)

6. In patients with chronic symptomatic HFrEF, treatment with an ARNi instead of

Value Statement: High
an ACEi provides high economic value.
Value (A)

7. ARNi should not be administered concomitantly with ACEi or within 36 hours of

3: Harm B-R
the last dose of an ACEi.

8. ARNi should not be administered to patients with any history of angioedema.

3: Harm C-LD

9. ACEi should not be administered to patients with any history of angioedema.

3: Harm C-LD

73
 Beta Blockers
Recommendation for Beta Blockers

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In patients with HFrEF, with current or previous symptoms, use of 1 of the 3 beta

1 A blockers proven to reduce mortality (e.g., bisoprolol, carvedilol, sustained-release

metoprolol succinate) is recommended to reduce mortality and hospitalizations.

Value Statement: 2. In patients with HFrEF, with current or previous symptoms, beta-blocker therapy

High Value (A) provides high economic value.

74
 Mineralocorticoid Receptor Antagonists (MRAs)
Recommendations for Mineralocorticoid Receptor Antagonists (MRAs)

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In patients with HFrEF and NYHA class II-IV symptoms, an

MRA (spironolactone or eplerenone) is recommended to reduce morbidity and

1 A mortality, if eGFR is >30 mL/min/1.73 m2 and serum potassium is <5.0 mEq/L. Careful

monitoring of potassium, renal function, and diuretic dosing should be performed at initiation

and closely monitored thereafter to minimize risk of hyperkalemia and renal insufficiency.
Value Statement: High 2. In patients with HFrEF and NYHA class II-IV symptoms, MRA therapy provides high

Value (A) economic value.

3. In patients taking MRA whose serum potassium cannot be maintained at <5.5 mEq/L, MRA
3: Harm B-NR
should be discontinued to avoid life-threatening hyperkalemia.

75
 Sodium-Glucose Cotransporter 2 Inhibitors
Recommendation for SGLT2i

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In patients with symptomatic chronic HFrEF, SGLT2i are recommended to

1 A reduce hospitalization for HF and cardiovascular mortality, irrespective of the

presence of type 2 diabetes.

Value Statement: 2. In patients with symptomatic chronic HFrEF, SGLT2i therapy provides

Intermediate Value intermediate economic value.

(A)

76
 Hydralazine and Isosorbide Dinitrate

Recommendations for Hydralazine and Isosorbide Dinitrate

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. For patients self-identified as African American with NYHA class III-IV HFrEF

who are receiving optimal medical therapy, the combination of hydralazine and
1 A
isosorbide dinitrate is recommended to improve symptoms and reduce morbidity

and mortality.

77
 Hydralazine and Isosorbide Dinitrate
(con’t.)

2. For patients self-identified as African American with NYHA class III-IV HFrEF who are

Value Statement: receiving optimal medical therapy with ACEi or ARB, beta blockers, and MRA, the

High Value (B-NR) combination of hydralazine and isosorbide dinitrate provides high economic value.

3. In patients with current or previous symptomatic HFrEF who cannot be given first-line

agents, such as ARNi, ACEi, or ARB, because of drug intolerance or renal insufficiency, a
2b C-LD
combination of hydralazine and isosorbide dinitrate might be considered to reduce

morbidity and mortality.

78
Figure 6.
Treatment of
HFrEF Stages
C and D

Colors correspond to COR in Table 2.

Treatment recommendations for

patients with HFrEF are displayed.
Step 1 medications may be started
simultaneously at initial (low)
doses recommended for HFrEF.
Alternatively, these medications
may be started sequentially, with
sequence guided by clinical or
other factors, without need to
achieve target dosing before
initiating next medication.
Medication doses should be
increased to target as tolerated.

79
 Other Drug Treatment

Recommendations for Other Drug Treatment

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HF class II to IV symptoms, omega-3 polyunsaturated fatty

2b B-R acid (PUFA) supplementation may be reasonable to use as adjunctive therapy

to reduce mortality and cardiovascular hospitalizations.

80
 Other Drug Treatment (con’t.)

2. In patients with HF who experience hyperkalemia (serum potassium level ≥5.5 mEq/L)

while taking a renin-angiotensin-aldosterone system inhibitor (RAASi), the effectiveness

2b B-R of potassium binders (patiromer, sodium zirconium cyclosilicate) to improve outcomes

by facilitating continuation of RAASi therapy is uncertain.

3. In patients with chronic HFrEF without a specific indication (e.g., venous

3: No thromboembolism [VTE], AF, a previous thromboembolic event, or a cardioembolic
B-R
Benefit source), anticoagulation is not recommended.

81
 Drugs of Unproven Value or That May
Worsen HF
Recommendations for Drugs of Unproven Value or Drugs That May Worsen HF

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

3: No 1. In patients with HFrEF, dihydropyridine calcium channel-blocking drugs are not

A
Benefit recommended treatment for HF.

3: No 2. In patients with HFrEF, vitamins, nutritional supplements, and hormonal therapy are
B-R
Benefit not recommended other than to correct specific deficiencies.

3. In patients with HFrEF, nondihydropyridine calcium channel-blocking drugs are not

3: Harm A
recommended.

82
 Drugs of Unproven Value or That May
Worsen HF (con’t.)

4. In patients with HFrEF, class IC antiarrhythmic medications and dronedarone may

3: Harm A
increase the risk of mortality.

5. In patients with HFrEF, thiazolidinediones increase the risk of worsening HF

3: Harm A
symptoms and hospitalizations.

6. In patients with type 2 diabetes and high cardiovascular risk, the dipeptidyl

3: Harm B-R peptidase-4 (DPP-4) inhibitors saxagliptin and alogliptin increase the risk of HF

hospitalization and should be avoided in patients with HF.

7. In patients with HFrEF, NSAIDs worsen HF symptoms and should be avoided or

3: Harm B-NR
withdrawn whenever possible.

83
 Table 13. Selected Prescription Medications That May
Cause or Exacerbate HF
Drug or Therapeutic Class Associated With HF Magnitude of HF Level of Evidence for Possible Mechanism(s) Onset
Causes Direct Exacerbates Induction or HF Induction or
Myocardial Toxicity Underlying Precipitation Precipitation
Myocardial

Dysfunction
COX, nonselective inhibitors X Major B Prostaglandin inhibition Immediate

(NSAIDs) leading to sodium and

COX, selective inhibitors X Major B water retention,
(COX-2 inhibitors) increased systemic

vascular resistance, and

blunted response to

diuretics

Thiazolidinediones X Major A Possible calcium Intermediate

channel blockade

84
 Table 13. Selected Prescription Medications That May Cause
or Exacerbate HF (con’t.)
Saxagliptin X Major A Unknown Intermediate to delayed
Alogliptin X Major A
Flecainide X Major A Negative inotrope, Immediate to intermediate
Disopyramide X Major B proarrhythmic effects
Sotalol X Major A Proarrhythmic Immediate to intermediate

properties, beta

blockade
Dronedarone X Major A Negative inotrope
Alpha-1 blockers
Doxazosin X Moderate B Beta-1-receptor Intermediate to delayed

stimulation with
COX indicates
cy clo-
increases in renin
oxygenase;
and HF, heart and aldosterone
failure.
Diltiazem X Major B Negative inotrope Immediate to intermediate
Verapamil X Major B
Nifedipine X Moderate C Negative inotrope Immediate to intermediate

85
 GDMT Dosing: Sequencing and Uptitration
Recommendations for GDMT Dosing: Sequencing and Uptitration

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HFrEF, titration of guideline-directed medication dosing to

achieve target doses showed to be efficacious in RCTs is recommended, to reduce

1 A
cardiovascular mortality and HF hospitalizations, unless not well tolerated.

2. In patients with HFrEF, titration and optimization of guideline-directed

medications as frequently as every 1 to 2 weeks depending on the patient’s

2a C-EO
symptoms, vital signs, and laboratory findings can be useful to optimize

management.

86
 Table 14. Drugs Commonly Used for HFrEF (Stage C HF)

Mean Doses Achieved in References

Drug Initial Daily Dose(s) Target Doses(s)
Clinical Trials
ACEi
Captopril 6.25 mg 3 times daily 50 mg 3 times daily 122.7 mg total daily (19)
Enalapril 2.5 mg twice daily 10–20 mg twice daily 16.6 mg total daily (3)
Fosinopril 5–10 mg once daily 40 mg once daily NA …
Lisinopril 2.5–5 mg once daily 20–40 mg once daily 32.5–35.0 mg total daily (17)
Perindopril 2 mg once daily 8–16 mg once daily NA …
Quinapril 5 mg twice daily 20 mg twice daily NA …
Ramipril 1.25–2.5 mg once daily 10 mg once daily NA …
Trandolapril 1 mg once daily 4 mg once daily NA …

87
 Table 14. Drugs Commonly Used for HFrEF (Stage C HF)
(con’t.)

ARB
Candesartan 4–8 mg once daily 32 mg once daily 24 mg total daily (20)
Losartan 25–50 mg once daily 50–150 mg once daily 129 mg total daily (18)
Valsartan 20–40 mg once daily 160 mg twice daily 254 mg total daily (21)
ARNi
49 mg sacubitril and 51 mg (22)

valsartan twice daily

97 mg sacubitril and 103 182 mg sacubitril and 193
Sacubitril-valsartan (therapy may be initiated at
mg valsartan twice daily mg valsartan total daily
24 mg sacubitril and 26 mg

valsartan twice daily)

88
 Table 14. Drugs Commonly Used for HFrEF (Stage C HF)
(con’t.)

Beta blockers
Bisoprolol 1.25 mg once daily 10 mg once daily 8.6 mg total daily (1)
Carvedilol 3.125 mg twice daily 25–50 mg twice daily 37 mg total daily (23)
Carvedilol CR 10 mg once daily 80 mg once daily NA …
Metoprolol succinate (11)

extended release 12.5–25 mg once daily 200 mg once daily 159 mg total daily

(metoprolol CR/XL)
Mineralocorticoid receptor antagonists
Spironolactone 12.5–25 mg once daily 25–50 mg once daily 26 mg total daily (6)
Eplerenone 25 mg once daily 50 mg once daily 42.6 mg total daily (13)

89
 Table 14. Drugs Commonly Used for HFrEF (Stage C HF)
(con’t.)

SGLT2i
Dapagliflozin 10 mg once daily 10 mg once daily 9.8 mg total daily (8)
Empagliflozin 10 mg once daily 10 mg once daily NR (9)
Isosorbide dinitrate and hydralazine
20 mg isosorbide dinitrate 40 mg isosorbide dinitrate 90 mg isosorbide dinitrate (10)

Fixed dose combination and 37.5 mg hydralazine 3 and 75 mg hydralazine 3 and ~175 mg hydralazine

times daily times daily total daily

Isosorbide dinitrate and 20–30 mg isosorbide 120 mg isosorbide dinitrate (24)

hydralazine dinitrate and 25–50 mg total daily in divided doses

NA
hydralazine 3–4 times daily and 300 mg hydralazine

total daily in divided doses

90
 Table 14. Drugs Commonly Used for HFrEF (Stage C HF)
(con’t.)

If Channel inhibitor
Ivabradine 5 mg twice daily 7.5 mg twice daily 12.8 total daily (25-27)
Soluble guanylate cyclase stimulator
Vericiguat 2.5 mg once daily 10 mg once daily 9.2 mg total daily (28)
Individualized variable (29, 30)
0.125–0.25 mg daily
dose to achieve serum
Digoxin (modified according to NA
digoxin concentration 0.5–
monogram)
<0.9 ng/mL

ACE indicates angiotensin-converting enzyme;

ARB, angiotensin receptor blocker; CR, controlled
release; CR/XL, controlled release/extended
release; HF, heart failure; HFrEF, heart failure with
reduced ejection fraction; NA, not applicable; NR,
not reported; and SGLT2i, sodium glucose
cotransporter 2 inhibitor.

91
 Table 15. Benefits of Evidence-Based Therapies for
Patients With HFrEF
Evidence-Based Therapy Relative Risk Reduction in All- NNT to Prevent All-Cause NNT for All-Cause Mortality NNT for All- Cause

Cause Mortality in Pivotal Mortality Over Time* (Standardized to 12 mo) Mortality (Standardized to

RCTs, % 36 mo)
ACEi or ARB 17 22 over 42 mo 77 26
ARNi† 16 36 over 27 mo 80 27
Beta blocker 34 28 over 12 mo 28 9
Mineralocorticoid receptor antagonist 30 9 over 24 mo 18 6
SGLT2i 17 43 over 18 mo 63 22
Hydralazine or nitrate‡ 43 25 over 10 mo 21 7
CRT 36 12 over 24 mo 24 8
ICD 23 14 over 60 mo 70 23

ACEi indicates angiotensin-converting enzyme inhibitor; ARB, *Median duration follow-up in the respective clinical trial.
angiotensin receptor blocker; ARNi, angiotensin receptor neprilysin †Benefit of ARNi therapy incremental to that achieved with ACEi therapy. For the other
inhibitor; CRT, cardiac resynchronization therapy; ICD, implantable medications shown, the benefits are based on comparisons to placebo control.
cardioverter-defibrillator; SGLT2i, sodium-glucose cotransporter-2 ‡Benefit of hydralazine-nitrate therapy was limited to African American patients in
inhibitor; and NNT, number needed to treat. this trial.

92
 Management of Stage C HF: Ivabradine

Recommendation for the Management of Stage C HF: Ivabradine

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. For patients with symptomatic (NYHA class II to III) stable chronic HFrEF

(LVEF ≤35%) who are receiving GDMT, including a beta blocker at

maximum tolerated dose, and who are in sinus rhythm with a heart rate of
2a B-R
≥70 bpm at rest, ivabradine can be beneficial to reduce HF hospitalizations

and cardiovascular death.

93
 Pharmacological Treatment for Stage C
HFrEF (Digoxin)

Recommendation for the Pharmacological Treatment for Stage C HFrEF (Digoxin)

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In patients with symptomatic HFrEF despite GDMT (or who are unable to tolerate

2b B-R GDMT), digoxin might be considered to decrease hospitalizations for HF.

94
Pharmacological Treatment for Stage C HFrEF:
Soluble Guanylyl Cyclase Stimulators

Recommendation for Pharmacological Treatment for Stage C HFrEF: Soluble Guanylyl Cyclase

Stimulators

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In selected high-risk patients with HFrEF and recent worsening of HF already

on GDMT, an oral soluble guanylate cyclase stimulator (vericiguat) may be

2b B-R
considered to reduce HF hospitalization and cardiovascular death.

95
Figure 7.
Additional
Medical
Therapies for
Patients With
HFrEF
Colors correspond to COR in Table 2

Recommendations for additional medical

therapies that may be considered for patients
with HF are shown.

GDMT indicates guideline-directed medical

therapy; HF, heart failure; HFH, heart failure
hospitalization; HFrEF, heart failure with reduced
ejection fraction; IV, intravenous; LVEF, left
ventricular ejection fraction; LVESD, left
ventricular end systolic dimension; MV, mitral
valve; MR, mitral regurgitation; NP, natriuretic
peptide; NSR, normal sinus rhythm; and NYHA,
New York Heart Association; RAASi, renin-
angiotensin-aldosterone system inhibitors.

96
 ICDs and CRTs
Recommendations for ICDs and CRTs

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In patients with nonischemic DCM or ischemic heart disease at least 40 days post-MI with

LVEF ≤35% and NYHA class II or III symptoms on chronic GDMT, who have reasonable
1 A
expectation of meaningful survival for >1 year, ICD therapy is recommended for primary

prevention of SCD to reduce total mortality.

2. A transvenous ICD provides high economic value in the primary prevention of SCD

Value Statement: High Value particularly when the patient’s risk of death caused by ventricular arrythmia is deemed high

(A) and the risk of nonarrhythmic death (either cardiac or noncardiac) is deemed low based on

the patient’s burden of comorbidities and functional status.

97
 ICDs and CRTs (con’t.)

3. In patients at least 40 days post-MI with LVEF ≤30% and NYHA class I symptoms while

1 B-R receiving GDMT, who have reasonable expectation of meaningful survival for >1 year, ICD

therapy is recommended for primary prevention of SCD to reduce total mortality.

4. For patients who have LVEF ≤35%, sinus rhythm, left bundle branch block (LBBB) with a

QRS duration ≥150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT,
1 B-R
CRT is indicated to reduce total mortality, reduce hospitalizations, and improve symptoms

and QOL.
5. For patients who have LVEF ≤35%, sinus rhythm, LBBB with a QRS duration of ≥150 ms,
Value Statement: High Value
and NYHA class II, III, or ambulatory IV symptoms on GDMT, CRT implantation provides
(B-NR)
high economic value.

98
 ICDs and CRTs (con’t.)

6. For patients who have LVEF ≤35%, sinus rhythm, a non-LBBB pattern with a QRS

duration ≥150 ms, and NYHA class II, III, or ambulatory class IV symptoms on GDMT,
2a B-R
CRT can be useful to reduce total mortality, reduce hospitalizations, and improve symptoms

and QOL.
7. In patients with high-degree or complete heart block and LVEF of 36% to 50%, CRT is

2a B-R reasonable to reduce total mortality, reduce hospitalizations, and improve symptoms and

QOL.
8. In patients with AF and LVEF ≤35% on GDMT, CRT can be useful to reduce total

mortality, improve symptoms and QOL, and increase LVEF, if: a) the patient requires
2a B-NR
ventricular pacing or otherwise meets CRT criteria and b) atrioventricular nodal ablation or

pharmacological rate control will allow near 100% ventricular pacing with CRT.

99
 ICDs and CRTs (con’t.)
9. For patients on GDMT who have LVEF ≤35% and are undergoing placement of a new

or replacement device implantation with anticipated requirement for significant (>40%)

2a B-NR
ventricular pacing, CRT can be useful to reduce total mortality, reduce hospitalizations,

and improve symptoms and QOL.

10. For patients who have LVEF ≤35%, sinus rhythm, LBBB with a QRS duration of 120 to

149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT, CRT can be
2a B-NR
useful to reduce total mortality, reduce hospitalizations, and improve symptoms and

QOL.
11. In patients with genetic arrhythmogenic cardiomyopathy with high-risk features of

2a B-NR sudden death, with EF ≤45%, implantation of ICD is reasonable to decrease sudden

death.

100
 ICDs and CRTs (con’t.)
12. For patients who have LVEF ≤35%, sinus rhythm, a non-LBBB pattern with QRS

duration of 120 to 149 ms, and NYHA class III or ambulatory class IV on GDMT, CRT

2b B-NR may be considered to reduce total mortality, reduce hospitalizations, and improve

symptoms and QOL.

13. For patients who have LVEF ≤30%, ischemic cause of HF, sinus rhythm, LBBB with a

QRS duration ≥150 ms, and NYHA class I symptoms on GDMT, CRT may be
2b B-NR
considered to reduce hospitalizations and improve symptoms and QOL.

14. In patients with QRS duration <120 ms, CRT is not recommended.
3: No Benefit B-R

101
 ICDs and CRTs (con’t.)

15. For patients with NYHA class I or II symptoms and non-LBBB pattern with
3: No
B-NR QRS duration <150 ms, CRT is not recommended (16-21, 28-33).
Benefit

16. For patients whose comorbidities or frailty limit survival with good

3: No functional capacity to <1 year, ICD and cardiac resynchronization therapy

C-LD
Benefit with defibrillation (CRT-D) are not indicated (1-9, 16-21).

102
Figure 8.
Algorithm for CRT
Indications in
Patients With
Cardiomyopathy
or HFrEF
Colors correspond to COR in Table 2.

Recommendations for cardiac

resynchronization therapy (CRT) are
displayed.
AF indicates atrial fibrillation; Amb,
ambulatory; CM, cardiomyopathy; GDMT,
guideline-directed medical therapy; HB,
heart block; HF, heart failure; HFrEF, heart
failure with reduced ejection fraction; LBBB,
left bundle branch block; LV, left
ventricular; LVEF, left ventricular ejection
fraction; NSR, normal sinus rhythm; NYHA,
New York Heart Association; and RV, right
ventricular.

103
 Revascularization for CAD

Recommendation for Revascularization for CAD

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In selected patients with HF, reduced EF (EF ≤35%), and suitable

coronary anatomy, surgical revascularization plus GDMT is beneficial

1 B-R
to improve symptoms, cardiovascular hospitalizations, and long-term

all-cause mortality.

104
Figure 9.
Additional Device
Therapies

Colors correspond to COR in Table 2.

Recommendations for additional

nonpharmaceutical interventions that may
be considered for patients with HF are
shown.

GDMT indicates guideline-directed medical

therapy; HF, heart failure; HFH, heart failure
hospitalization; HFrEF, heart failure with
reduced ejection fraction; IV, intravenous;
LVEF, left ventricular ejection fraction;
LVESD, left ventricular end systolic
dimension; MV, mitral valve; MR, mitral
regurgitation; NP, natriuretic peptide; NSR,
normal sinus rhythm; NYHA, New York Heart
Association; and PASP, pulmonary artery
systolic pressure.

105
 Valvular Heart Disease

Recommendations for Valvular Heart Disease

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HF, VHD should be managed in a multidisciplinary manner in

1 B-R accordance with clinical practice guidelines for VHD to prevent worsening of HF

and adverse clinical outcomes.

2. In patients with chronic severe secondary MR and HFrEF, optimization of GDMT

1 C-LD is recommended before any intervention for secondary MR related to LV

dysfunction.

106
Figure 10.
Treatment
Approach in
Secondary Mitral
Regurgitation

Colors correspond to Table 2

107
 HF With Mildly Reduced Ejection Fraction
Recommendations for HF With Mildly Reduced Ejection Fraction

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with HFmrEF, SGLT2i can be beneficial in decreasing HF

2a B-R
hospitalizations and cardiovascular mortality.

2. Among patients with current or previous symptomatic HFmrEF (LVEF 41%–

49%), use of evidence-based beta blockers for HFrEF, ARNi, ACEi or ARB, and

2b B-NR MRAs may be considered to reduce the risk of HF hospitalization and

cardiovascular mortality, particularly among patients with LVEF on the lower end

of this spectrum.

108
Figure 11.
Recommendations
for Patients With
Mildly Reduced
LVEF (41%–49%)

Colors correspond to COR in Table 2.

Medication recommendations for HFmrEF are

displayed.

ACEi indicates angiotensin-converting

enzyme inhibitor; ARB, angiotensin receptor
blocker; ARNi, angiotensin receptor-
neprilysin inhibitor; HRmrEF, heart failure
with mildly reduced ejection fraction; HFrEF,
heart failure with reduced ejection fraction;
LVEF, left ventricular ejection fraction; MRA,
mineralocorticoid receptor antagonist; and
SGLT2i, sodium- glucose cotransporter 2
inhibitor.

109
 HF With Improved Ejection Fraction

Recommendation for HF With Improved Ejection Fraction

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

COR LOE Recommendation

1. In HFimpEF after treatment, GDMT should be continued to prevent relapse of HF

1 B-R and LV dysfunction, even in patients who may become asymptomatic.

110
 HF With Preserved Ejection Fraction
Recommendations for HF With Preserved Ejection Fraction*

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. Patients with HFpEF and hypertension should have medication titrated to

attain blood pressure targets in accordance with published clinical practice

1 C-LD
guidelines to prevent morbidity.

2. In patients with HFpEF, SGLT2i can be beneficial in decreasing HF

2a B-R
hospitalizations and cardiovascular mortality.

3. In patients with HFpEF, management of AF can be useful to improve

2a C-EO
symptoms.

111
 HF With Preserved Ejection Fraction (con’t.)
4. In selected patients with HFpEF, MRAs may be considered to decrease

2b B-R hospitalizations, particularly among patients with LVEF on the lower end of this

spectrum.
5. In selected patients with HFpEF, the use of ARB may be considered to decrease

2b B-R hospitalizations, particularly among patients with LVEF on the lower end of this

spectrum.
6. In selected patients with HFpEF, ARNi may be considered to decrease

2b B-R hospitalizations, particularly among patients with LVEF on the lower end of this

spectrum.
7. In patients with HFpEF, routine use of nitrates or phosphodiesterase-5 inhibitors to
3: No-
B-R
increase activity or QOL is ineffective.
Benefit

112
Figure 12.
Recommendations
for Patients With
Preserved LVEF
(≥50%)

Colors correspond to COR in Table 2.

Medication recommendations for HFpEF are

displayed.

*Greater benefit in patients with LVEF closer

to 50%.

ARB indicates angiotensin receptor blocker;

ARNi, angiotensin receptor-neprilysin
inhibitor; HF, heart failure; HFpEF, heart
failure with preserved ejection fraction; LVEF,
left ventricular ejection fraction; MRA,
mineralocorticoid receptor antagonist; and
SGLT2i, sodium-glucose cotransporter 2
inhibitor.

113
 Diagnosis of Cardiac Amyloidosis
Recommendations for Diagnosis of Cardiac Amyloidosis

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. Patients for whom there is a clinical suspicion for cardiac amyloidosis* should have

1 B-NR screening for serum and urine monoclonal light chains with serum and urine *LV wall thickness
≥14 mm in
conjunction with
immunofixation electrophoresis and serum free light chains. fatigue, dyspnea,
or edema,
especially in the
2. In patients with high clinical suspicion for cardiac amyloidosis, without evidence of context of
discordance
between wall
1 B-NR serum or urine monoclonal light chains, bone scintigraphy should be performed to thickness on
echocardiogram
and QRS voltage
confirm the presence of transthyretin cardiac amyloidosis. on ECG, and in
the context of
aortic stenosis,
3. In patients for whom a diagnosis of transthyretin cardiac amyloidosis is made, genetic HFpEF, carpal
tunnel syndrome,
spinal stenosis,
1 B-NR testing with TTR gene sequencing is recommended to differentiate hereditary variant and autonomic or
sensory
polyneuropathy.
from wild-type transthyretin cardiac amyloidosis.

114
 Treatment of Cardiac Amyloidosis
Recommendations for Treatment of Cardiac Amyloidosis

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In select patients with wild-type or variant transthyretin cardiac amyloidosis and NYHA class I

1 B-R to III HF symptoms, transthyretin tetramer stabilizer therapy (tafamidis) is indicated to reduce

cardiovascular morbidity and mortality.

Value Statement: Low 2. At 2020 list prices, tafamidis provides low economic value (>$180,000 per QALY gained) in

Value (B-NR) patients with HF with wild-type or variant transthyretin cardiac amyloidosis.
3. In patients with cardiac amyloidosis and AF, anticoagulation is reasonable to reduce the risk of

stroke regardless of the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years,
2a C-LD
diabetes mellitus, stroke or transient ischemic attack [TIA], vascular disease, age 65 to 74 years,

sex category) score .

115
Figure 13. Diagnostic
and Treatment of
Transthyretin
Cardiac Amyloidosis
Algorithm
Colors correspond to COR in Table 2.

AF indicates atrial fibrillation; AL-CM, AL

amyloid cardiomyopathy; ATTR-CM,
transthyretin amyloid cardiomyopathy; ATTRv,
variant transthyretin amyloidosis; ATTRwt, wild-
type transthyretin amyloidosis; CHA2DS2-VASc,
congestive heart failure, hypertension, age ≥75
years, diabetes mellitus, stroke or transient
ischemic attack (TIA), vascular disease, age 65 to
74 years, sex category; ECG, electrocardiogram;
H/CL, heart to contralateral chest; HFrEF, heart
failure with reduced ejection fraction; IFE,
immunofixation electrophoresis; MRI, magnetic
resonance imaging; NYHA, New York Heart
Association; PYP, pyrophosphate; Tc,
technetium; and TTR, transthyretin.

116
Stage D (Advanced) HF

117
 Specialty Referral for Advanced HF

Recommendation for Specialty Referral for Advanced HF

COR LOE Recommendation

1. In patients with advanced HF, when consistent with the patient’s goals of

care, timely referral for HF specialty care is recommended to review HF

1 C-LD management and assess suitability for advanced HF therapies (e.g., LVAD,

cardiac transplantation, palliative care, and palliative inotropes).

118
Table 16. ESC Definition of Advanced HF

All of these criteria must be present despite optimal guideline-

directed treatment:
1. Severe and persistent symptoms of HF (NYHA class III

[advanced] or IV)
2. Severe cardiac dysfunction defined by ≥1 of these:
• LVEF ≤30%
• Isolated RV failure
• Nonoperable severe valve abnormalities
• Nonoperable severe congenital heart disease
• EF ≥40%, elevated natriuretic peptide levels

and evidence of significant diastolic

dysfunction

119
 Table 16. ESC Definition of Advanced HF (con’t.)

3. Hospitalizations or unplanned visits in the past 12 mo for episodes of:

• Congestion requiring high-dose intravenous diuretics or diuretic

combinations
• Low output requiring inotropes or vasoactive medications

• Malignant arrhythmias
4. Severe impairment of exercise capacity with inability to exercise or low 6-minute walk test

EF indicates ejection distance (<300 m) or peak VO2 (<12–14 mL/kg/min) estimated to be of cardiac origin
fraction; ESC, European
Society of Cardiology; HF,
heart failure; LVEF, left Criteria 1 and 4 can be met in patients with cardiac dysfunction (as described in criterion 2) but who
ventricular ejection
fraction; NYHA, New York
Heart Association; RV, right also have substantial limitations as a result of other conditions (e.g., severe pulmonary disease,
ventricular; and VO2,
oxygen
consumption/oxygen noncardiac cirrhosis, renal disease). The therapeutic options for these patients may be more limited.
uptake.
Adapted from Crespo-Leiro
et al.

120
 Table 17. INTERMACS Profiles

Profile∗ Profile Description Features

1 Critical cardiogenic shock Life-threatening hypotension and rapidly escalating inotropic/pressor support, with

critical organ hypoperfusion often confirmed by worsening acidosis and lactate

levels.

2 Progressive decline “Dependent” on inotropic support but nonetheless shows signs of continuing

deterioration in nutrition, renal function, fluid retention, or other major status

indicator. Can also apply to a patient with refractory volume overload, perhaps with

evidence of impaired perfusion, in whom inotropic infusions cannot be maintained

because of tachyarrhythmias, clinical ischemia, or other intolerance.

121
 Table 17. INTERMACS Profiles (con’t.)

Profile∗ Profile Description Features

3 Stable but inotrope Clinically stable on mild-moderate doses of intravenous inotropes (or has a temporary

dependent circulatory support device) after repeated documentation of failure to wean without symptomatic

hypotension, worsening symptoms, or progressive organ dysfunction (usually renal).

4 Resting symptoms on oral Patient who is at home on oral therapy but frequently has symptoms of congestion at rest or with

therapy at home activities of daily living (dressing or bathing). He or she may have orthopnea, shortness of

breath during dressing or bathing, gastrointestinal symptoms (abdominal discomfort, nausea,

poor appetite), disabling ascites, or severe lower extremity edema.

5 Exertion intolerant Patient who is comfortable at rest but unable to engage in any activity, living predominantly

within the house or housebound.

122
 Table 17. INTERMACS Profiles (con’t.)

Profile∗ Profile Description Features

6 Exertion limited Patient who is comfortable at rest without evidence of fluid overload but who is able to do some

mild activity. Activities of daily living are comfortable, and minor activities outside the home

such as visiting friends or going to a restaurant can be performed, but fatigue results within a

few minutes or with any meaningful physical exertion.

7 Advanced NYHA class III Patient who is clinically stable with a reasonable level of comfortable activity, despite a history

of previous decompensation that is not recent. This patient is usually able to walk more than a

block. Any decompensation requiring intravenous diuretics or hospitalization within the

previous month should make this person a Patient Profile 6 or lower.

123
Table 17. INTERMACS Profiles (con’t.)

ICD indicates implantable cardioverter-defibrillator;

INTERMACS, Interagency Registry for Mechanically Assisted

Circulatory Support; and NYHA, New York Heart Association.

124
 Table 18. Clinical Indicators of Advanced HF

Repeated hospitalizations or emergency department visits for HF in the past 12 mo.

Need for intravenous inotropic therapy.

Persistent NYHA functional class III to IV symptoms despite therapy.

Severely reduced exercise capacity (peak VO2, <14 mL/kg/min or <50% predicted, 6-minute walk test distance

<300 m, or inability to walk 1 block on level ground because of dyspnea or fatigue).

Intolerance to RAAS inhibitors because of hypotension or worsening renal function.

Intolerance to beta blockers as a result of worsening HF or hypotension.

Recent need to escalate diuretics to maintain volume status, often reaching daily furosemide equivalent dose >160

mg/d or use of supplemental metolazone therapy.

125
 Table 18. Clinical Indicators of Advanced HF
(con’t.)

Refractory clinical congestion.

Progressive deterioration in renal or hepatic function.

Worsening right HF or secondary pulmonary hypertension.

HF indicates heart
failure; ICD, implantable
cardioverter- Frequent SBP ≤90 mm Hg.
defibrillator; MAGGIC,
Meta-analysis Global
Group in Chronic Heart Cardiac cachexia.
Failure; NYHA, New York
Heart Association; RAAS,
renin-angiotensin-
aldosterone system; SBP,
Persistent hyponatremia (serum sodium, <134 mEq/L).
systolic blood pressure;
SHFM, Seattle Heart
Failure model; and VO2, Refractory or recurrent ventricular arrhythmias; frequent ICD shocks.
oxygen
consumption/oxygen
uptake. Increased predicted 1-year mortality (e.g., >20%) according to HF survival models (e.g., MAGGIC, SHFM).

126
 Table 19. Indications and Contraindications
to Durable Mechanical Support

Indications (combination of these):

• Frequent hospitalizations for HF

• NYHA class IIIb to IV functional limitations despite maximal therapy

• Intolerance of neurohormonal antagonists

• Increasing diuretic requirement

• Symptomatic despite CRT

• Inotrope dependence

• Low peak VO2 (<14–16)

• End-organ dysfunction attributable to low cardiac output

127
 Table 19. Indications and Contraindications
to Durable Mechanical Support (con’t.)

Contraindications:

Absolute

• Irreversible hepatic disease

• Irreversible renal disease

• Irreversible neurological disease

• Medical nonadherence

• Severe psychosocial limitations

128
 Relative

• Age >80 y for destination therapy

Table 19. • Obesity or malnutrition

Indications and
Contraindications • Musculoskeletal disease that impairs rehabilitation

to Durable • Active systemic infection or prolonged intubation

Mechanical
Support (con’t.) • Untreated malignancy

• Severe PVD

• Active substance abuse

• Impaired cognitive function

CRT indicates cardiac
resynchronization therapy;
HF, heart failure; NYHA, New • Unmanaged psychiatric disorder
York Heart Association; VO2,
oxygen consumption; and
PVD, peripheral vascular
disease. • Lack of social support

129
 Nonpharmacological Management:
Advanced HF
Recommendation for Nonpharmacological Management: Advanced HF

COR LOE Recommendation

1. For patients with advanced HF and hyponatremia, the benefit of fluid

restriction to reduce congestive symptoms is uncertain.

2b C-LD

130
 Inotropic Support
Recommendations for Inotropic Support

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In patients with advanced (stage D) HF refractory to GDMT and device

2a B-NR therapy who are eligible for and awaiting MCS or cardiac transplantation,

continuous intravenous inotropic support is reasonable as “bridge therapy”.

2. In select patients with stage D HF, despite optimal GDMT and device

therapy who are ineligible for either MCS or cardiac transplantation,

2b B-NR
continuous intravenous inotropic support may be considered as palliative

therapy for symptom control and improvement in functional status.

3. In patients with HF, long-term use of either continuous or intermittent

3: Harm B-R intravenous inotropic agents, for reasons other than palliative care or as a

bridge to advanced therapies, is potentially harmful.

131
 Table 20. Intravenous Inotropic Agents Used
in the Management of HF

Inotropic Agent Dose (mcg/kg) Drug Kinetics Effects Adverse Effects Special

Bolus Infusion and CO HR SVR PVR Considerations

(/min) Metabolism

Adrenergic agonists

Dopamine NA 5–10 t1/2: 2–20 min ↑ ↑ ↔ ↔ T, HA, N, tissue Caution: MAO-I

NA 10–15 ↑ ↑ ↑ ↔ necrosis
R, H, P

Dobutamine NA 2.5–20 t1/2: 2–3 min H ↑/↓BP, HA, T, N, F, Caution: MAO-I;

↑ ↑ ↔ ↔ hypersensitivity CI: sulfite allergy

132
 Table 20. Intravenous Inotropic Agents Used
in the Management of HF (con’t.)

PDE 3 inhibitor

Milrinone NR 0.125–0.75 t1/2: 2.5 h ↑ ↑ ↓ ↓ T, ↓BP Accumulation may

H occur in setting of renal

failure; monitor kidney

function and LFTs

133
 Table 20. Intravenous Inotropic Agents Used
in the Management of HF (con’t.)

Vasopressors

Epinephrine NR 5–15 mcg/min t1/2: 2–3 min ↑ ↑ ↑ (↓) ↔ HA, T Caution: MAO-I

15–20 mcg/min t1/2: 2–3 min ↑ ↑↑ ↑↑ ↔ HA, T, Caution: MAO-I

Norepinephrine NR 0.5–30 mcg/min t1/2: 2.5 min ↔ ↑ ↑↑ ↔ ↓ HR, tissue necrosis Caution: MAO-I

BP indicates blood pressure; CI, contraindication; CO, cardiac output; F, fever; H, hepatic; HA, Up arrow means increase.
headache; HF, heart failure; HR, heart rate; LFT, liver function test; MAO-I, monoamine oxidase Side arrow means no change.
inhibitor; N, nausea; NA, not applicable; NR, not recommended; P, plasma; PDE, phosphodiesterase; Down arrow means decrease.
PVR, pulmonary vascular resistance; R, renal; SVR, systemic vascular resistance; T, tachyarrhythmias; Up/down arrow means either increase or decrease.
and t1/2, elimination half-life.

134
 Mechanical Circulatory Support
Recommendations for Mechanical Circulatory Support

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In select patients with advanced HFrEF with NYHA class IV symptoms

who are deemed to be dependent on continuous intravenous inotropes or

1 A
temporary MCS, durable LVAD implantation is effective to improve

functional status, QOL, and survival.

2. In select patients with advanced HFrEF who have NYHA class IV

symptoms despite GDMT, durable MCS can be beneficial to improve

2a B-R
symptoms, improve functional class, and reduce mortality.

135
 Mechanical Circulatory Support
3. In patients with advanced HFrEF who have NYHA class IV symptoms
Value Statement:
despite GDMT, durable MCS devices provide low to intermediate economic
Uncertain Value (B-
value based on current costs and outcomes.
NR)

4. In patients with advanced HFrEF and hemodynamic compromise and

shock, temporary MCS, including percutaneous and extracorporeal

2a B-NR ventricular assist devices, are reasonable as a “bridge to recovery” or

“bridge to decision”.

136
 Cardiac Transplantation
Recommendation for Cardiac Transplantation

COR LOE Recommendation

1. For selected patients with advanced HF despite GDMT, cardiac transplantation is

1 C-LD
indicated to improve survival and QOL (1-3).

2. In patients with stage D (advanced) HF despite GDMT, cardiac transplantation

Value Statement:
provides intermediate economic value (4).
Intermediate Value

(C-LD)

137
Patients Hospitalized With
Acute Decompensated HF

138
 Assessment of Patients Hospitalized
With Decompensated HF
Recommendations for Assessment of Patients Hospitalized With Decompensated HF

1. In patients hospitalized with HF, severity of congestion and adequacy of

1 C-LD
perfusion should be assessed to guide triage and initial therapy.

2. In patients hospitalized with HF, the common precipitating factors and the

1 C-LD overall patient trajectory should be assessed to guide appropriate therapy.

Goals for Optimization and Continuation of GDMT

3. For patients admitted with HF, treatment should address reversible factors,

1 C-LD establish optimal volume status, and advance GDMT toward targets for

outpatient therapy.

139
 ACS
Uncontrolled hypertension

Table 21. AF and other arrhythmias

Common Factors Additional cardiac disease (e.g., endocarditis)

Precipitating HF
Hospitalization Acute infections (e.g., pneumonia, urinary tract)
With Acute
Decompensated Nonadherence with medication regimen or dietary intake
HF
Anemia
Hyper- or hypothyroidism
Medications that increase sodium retention (e.g., NSAID)

ACS indicates acute coronary

syndrome; AF, atrial
fibrillation; and NSAID, Medications with negative inotropic effect (e.g., verapamil)
nonsteroidal anti-
inflammatory drug.

140
 Maintenance or Optimization of
GDMT During Hospitalization
Recommendations for Maintenance or Optimization of GDMT During Hospitalization

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In patients with HFrEF requiring hospitalization, preexisting GDMT should be
1 B-NR
continued and optimized to improve outcomes, unless contraindicated.
2. In patients experiencing mild decrease of renal function or asymptomatic reduction of

1 B-NR blood pressure during HF hospitalization, diuresis and other GDMT should not

routinely be discontinued.
3. In patients with HFrEF, GDMT should be initiated during hospitalization after
1 B-NR
clinical stability is achieved.
4. In patients with HFrEF, if discontinuation of GDMT is necessary during
1 B-NR
hospitalization, it should be reinitiated and further optimized as soon as possible.

141
 Diuretics in Hospitalized Patients:
Decongestion Strategy

Recommendations for Diuretics in Hospitalized Patients: Decongestion Strategy

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. Patients with HF admitted with evidence of significant fluid overload should be

1 B-NR promptly treated with intravenous loop diuretics to improve symptoms and reduce

morbidity.
2. For patients hospitalized with HF, therapy with diuretics and other guideline-

directed medications should be titrated with a goal to resolve clinical evidence of

1 B-NR
congestion to reduce symptoms and rehospitalizations.

142
 Diuretics in Hospitalized Patients:
Decongestion Strategy (con’t.)

3. For patients requiring diuretic treatment during hospitalization for HF, the

1 B-NR discharge regimen should include a plan for adjustment of diuretics to decrease

rehospitalizations.

4. In patients hospitalized with HF when diuresis is inadequate to relieve

symptoms and signs of congestion, it is reasonable to intensify the diuretic

regimen using either:

2a B-NR
a. higher doses of intravenous loop diuretics; or

b. addition of a second diuretic.

143
 Parenteral Vasodilation Therapy in
Patients Hospitalized With HF

Recommendation for Parenteral Vasodilation Therapy in Patients Hospitalized With HF

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

Recommendation
COR LOE

1. In patients who are admitted with decompensated HF, in the absence of systemic

hypotension, intravenous nitroglycerin or nitroprusside may be considered as an

2b B-NR
adjuvant to diuretic therapy for relief of dyspnea.

144
 VTE Prophylaxis in Hospitalized
Patients
Recommendation for VTE Prophylaxis in Hospitalized Patients

Referenced studies that support the recommendation are summarized in the Online Data Supplements.

Recommendation
COR LOE

1. In patients hospitalized with HF, prophylaxis for VTE is recommended to

prevent venous thromboembolic disease.

1 B-R

145
 Evaluation and Management of
Cardiogenic Shock
Recommendations for Evaluation and Management of Cardiogenic Shock

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with cardiogenic shock, intravenous inotropic support should

1 B-NR be used to maintain systemic perfusion and preserve end-organ

performance.

2. In patients with cardiogenic shock, temporary MCS is reasonable when

2a B-NR end-organ function cannot be maintained by pharmacologic means to

support cardiac function.

146
 Evaluation and Management of
Cardiogenic Shock (con’t.)
3. In patients with cardiogenic shock, management by a multidisciplinary team

2a B-NR experienced in shock in reasonable.

4. In patients presenting with cardiogenic shock, placement of a PA line may be

2b B-NR considered to define hemodynamic subsets and appropriate management

strategies.

5. For patients who are not rapidly responding to initial shock measures, triage

2b C-LD to centers that can provide temporary MCS may be considered to optimize

management.

147
Table 22. Suggested Shock Clinical Criteria*

SBP <90 mm Hg for >30 min:

a. Or mean BP <60 mm Hg for >30 min
b. Or requirement of vasopressors to maintain systolic BP

≥90 mm Hg or mean BP ≥60 mm Hg

Hypoperfusion defined by:
c. Decreased mentation
d. Cold extremities, livedo reticularis
e. Urine output <30 mL/h
f. Lactate >2 mmol/L

BP indicates blood pressure; and SBP, systolic blood pressure.

*Systolic BP and hypoperfusion criteria need to be met for

the shock diagnosis.

148
 Table 23. Suggested Shock Hemodynamic Criteria*

1. SBP <90 mm Hg or mean BP <60 mm Hg

2. Cardiac index <2.2 L/min/m2
3. Pulmonary capillary wedge pressure >15 mm Hg
4. Other hemodynamic considerations

a. Cardiac power output ([CO x MAP]/451) <0.6 W

b. Shock index (HR/systolic BP) >1.0

BP indicates blood pressure; CO, cardiac output;

CVP, central venous pressure; HR, heart rate; c. RV shock
MAP, mean arterial pressure; PADP, pulmonary
artery diastolic pressure; PASP, pulmonary i. Pulmonary artery pulse index [(PASP-
artery systolic pressure; PCW, pulmonary
capillary wedge; RV, right ventricular; and SBP,
systolic blood pressure. PADP)/CVP] <1.0

*Diagnosis of shock requires ≥1 criteria to be i. CVP >15 mm Hg

present along with cardiac index <2.0 L/min/m2
and SBP <90 mm Hg. i. CVP-PCW >0.6

149
 Table 24. Society for Cardiovascular Angiography
and Interventions (SCAI) Cardiogenic Shock Criteria

Stage Bedside Findings Selected Laboratory Hemodynamics

Markers
A: At risk --Normal venous pressure --Normal renal function --SBP >100 mm Hg

--Clear lungs --Normal lactate --Hemodynamics: Normal

--Normotensive --Warm extremities

--Normal perfusion --Strong palpable pulses

--Cause for risk for --Normal mentation

shock such as large

myocardial infarction

or HF

150
Table 24. Society for Cardiovascular Angiography and
Interventions (SCAI) Cardiogenic Shock Criteria (con’t.)

B: Beginning --Elevated venous --Preserved renal a) SBP <90 mm Hg

shock (“pre- pressure function b) MAP <60 mm Hg or

shock”) --Rales present --Normal lactate c) >30 mm Hg decrease

--Warm extremities --Elevated BNP from baseline SBP

--Hypotension --Strong pulses --HR >100 bpm

--Normal --Normal mentation --Hemodynamics: CI ≥2.2

perfusion L/min/m2

151
Table 24. Society for Cardiovascular Angiography and
Interventions (SCAI) Cardiogenic Shock Criteria (con’t.)

C: Classic --Elevated venous --Impaired renal --SBP <90 mm Hg; MAP

cardiogenic pressure function <60 mm Hg; >30 mm Hg

shock --Rales present --Increased lactate from baseline SBP despite

--Cold, ashen, livedo --Elevated BNP drugs and temporary

--Hypotension --Weak or nonpalpable --Increased LFTs MCS

--Hypoperfusion pulses --Acidosis --HR >100 bpm

--Altered mentation --Hemodynamics: CI ≤2.2

--Decreased urine L/min/m2; PCW >15 mm

output Hg; CPO <0.6 W; PAPi

--Respiratory distress <2.0; CVP-PCW >1.0

152
 Table 24. Society for Cardiovascular Angiography and
Interventions (SCAI) Cardiogenic Shock Criteria (con’t.)

D: Deteriorating Same as stage C --Persistent or Escalating use of pressors or

--Worsening worsening values of MCS to maintain SBP and

hypotension stage C end-organ perfusion in

BNP indicates brain
natriuretic peptide; CI, --Worsening setting of stage C
cardiac index; CPO,
cardiac power output;
CPR, cardiopulmonary hypoperfusion hemodynamics
resuscitation; CVP,
central venous pressure;
HR, heart rate; LFT, liver
function test; MAP,
mean arterial blood E: Extremis --Cardiac arrest --Worsening values of --SBP only with resuscitation
pressure; MCS,
mechanical circulatory
support; PAPi, --Refractory --CPR stage C laboratories --PEA
pulmonary artery
pulsatility index; PCW,
pulmonary capillary hypotension --Recurrent VT/VF
wedge pressures; PEA,
pulseless electrical
activity; SBP, systolic --Refractory
blood pressure; VF,
ventricular fibrillation;
and VT, ventricular hypoperfusion
tachycardia.

153
 Integration of Care: Transitions and
Team-Based Approaches

Recommendations for Integration of Care: Transitions and Team-Based Approaches

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients with high-risk HF, particularly those with recurrent hospitalizations for

HFrEF, referral to multidisciplinary HF disease management programs is

1 B-R
recommended to reduce the risk of hospitalization.

154
 Integration of Care: Transitions and
Team-Based Approaches (con’t.)
2. In patients hospitalized with worsening HF, patient-centered discharge

1 B-NR instructions with a clear plan for transitional care should be provided before

hospital discharge.

3. In patients hospitalized with worsening HF, participation in systems that allow

benchmarking to performance measures is reasonable to increase use of

2a B-NR
evidence-based therapy, and to improve quality of care.

4. In patients being discharged after hospitalization for worsening HF, an early

follow-up, generally within 7 days of hospital discharge, is reasonable to

2a B-NR
optimize care and reduce rehospitalization.

155
 A transitional care plan, communicated with the patient and their outpatient clinicians before hospital discharge, should clearly outline plans

for:

• Addressing any precipitating causes of worsening HF identified in the hospital;

Table 25. • Adjusting diuretics based on volume status (including weight) and electrolytes;
Important • Coordination of safety laboratory checks (e.g., electrolytes after initiation or intensification of GDMT);
Components • Further changes to optimize GDMT, including:
of a a. Plans for resuming medications held in the hospital;
Transitional b. Plans for initiating new medications;
Care Plan c. Plans for titration of GDMT to goal doses as tolerated;

• Reinforcing HF education and assessing compliance with medical therapy and lifestyle modifications, including dietary restrictions and

physical activity;

• Addressing high-risk characteristics that may be associated with poor postdischarge clinical outcomes, such as:

a. Comorbid conditions (e.g., renal dysfunction, pulmonary disease, diabetes, mental health, and substance use disorders);

b. Limitations in psychosocial support;

GDMT indicates c. Impaired health literacy, cognitive impairment;

guideline-directed
medical therapy; • Additional surgical or device therapy, referral to cardiac rehabilitation in the future, where appropriate;
and HF, heart
failure. • Referral to palliative care specialists and/or enrollment in hospice in selected patients.

156
Comorbidities in Patients With HF

157
 Management of Comorbidities in
Patients With HF

Recommendations for the Management of Comorbidities in Patients With HF

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

Management of Anemia or Iron Deficiency
1. In patients with HFrEF and iron deficiency with or without anemia,

2a B-R intravenous iron replacement is reasonable to improve functional status

and QOL.

2. In patients with HF and anemia, erythropoietin-stimulating agents should

3: Harm B-R
not be used to improve morbidity and mortality.

158
 Management of Comorbidities in
Patients With HF (con’t.)

Management of Hypertension

3. In patients with HFrEF and hypertension, uptitration of GDMT to the

1 C-LD
maximally tolerated target dose is recommended.

Management of Sleep Disorders

4. In patients with HF and suspicion of sleep-disordered breathing, a formal sleep

assessment is reasonable to confirm the diagnosis and differentiate between

2a C-LD
obstructive and central sleep apnea.

159
 Management of Comorbidities in
Patients With HF (con’t.)
5. In patients with HF and obstructive sleep apnea, continuous positive

airway pressure may be reasonable to improve sleep quality and decrease

2a B-R
daytime sleepiness.

6. In patients with NYHA class II to IV HFrEF and central sleep apnea,

3: Harm B-R
adaptive servo-ventilation causes harm.

Management of Diabetes

7. In patients with HF and type 2 diabetes, the use of SGLT2i is

1 A recommended for the management of hyperglycemia and to reduce HF-

related morbidity and mortality.

160
 ACEi indicates

Figure 14.
angiotensin-converting
enzyme inhibitor; AF,
atrial fibrillation; ARB,
Recommendations angiotensin receptor
blocker; AV,

for Treatment of atrioventricular;

CHA2DS2-VASc,

Patients With HF
congestive heart failure,
hypertension, age ≥75
years, diabetes mellitus,
and Selected stroke or transient
ischemic attack [TIA],

Comorbidities vascular disease, age 65

to 74 years, sex category;
CPAP, continuous positive
airway pressure; CRT,
cardiac resynchronization
Colors correspond to COR in Table 2. therapy; EF, ejection
fraction; GDMT,
guideline-directed
medical therapy; HF,
heart failure; HFrEF, heart
failure with reduced
ejection fraction; IV,
Recommendations for treatment of intravenous; LVEF, left
patients with HF and select ventricular ejection
comorbidities are displayed. fraction; NYHA, New York
*Patients with chronic HF with Heart Association; SGLT2i,
permanent-persistent-paroxysmal sodium-glucose
AF and a CHA2DS2-VASc score of ≥2 cotransporter 2 inhibitor;
(for men) and ≥3 (for women). and VHD, valvular heart
disease.

161
 Table 26. Most Common Co-Occurring Chronic Conditions
Among Medicare Beneficiaries With HF (N=4,947,918), 2011

Beneficiaries Age ≥65 y (n=4,376,150)∗ Beneficiaries Age <65 y (n=571,768)†

n % n %

Hypertension 3,685,373 84.2 Hypertension 461,235 80.7

Ischemic heart
Ischemic heart disease 3,145,718 71.9 365,889 64.0
disease

Hyperlipidemia 2,623,601 60.0 Diabetes 338,687 59.2

Anemia 2,200,674 50.3 Hyperlipidemia 325,498 56.9

162
 Table 26. Most Common Co-Occurring Chronic Conditions
Among Medicare Beneficiaries With HF (N=4,947,918), 2011
(con’t.)

Diabetes 2,027,875 46.3 Anemia 284,102 49.7

Arthritis 1,901,447 43.5 CKD 257,015 45.0

CKD 1,851,812 42.3 Depression 207,082 36.2

COPD 1,311,118 30.0 Arthritis 201,964 35.3

AF indicates
atrial
fibrillation; CKD, AF 1,247,748 28.5 COPD 191,016 33.4
chronic kidney
disease; COPD, ∗Mean No. of
chronic conditions is 6.1;
obstructive median is 6.
pulmonary
disease; and HF,
Alzheimer’s disease or dementia 1,207,704 27.6 Asthma 88,816 15.5 †Mean No. of
conditions is 5.5;
heart failure. median is 5.

163
 Management of AF in HF
Recommendations for Management of AF in HF

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. Patients with chronic HF with permanent-persistent-paroxysmal AF and a

1 A CHA2DS2-VASc score of ≥2 (for men) and ≥3 (for women) should receive chronic

anticoagulant therapy.
2. For patients with chronic HF with permanent-persistent-paroxysmal AF, DOAC

1 A is recommended over warfarin in eligible patients.

164
 Management of AF in HF (con’t.)
3. For patients with HF and symptoms caused by AF, AF ablation is reasonable to
2a B-R improve symptoms and QOL.

4. For patients with AF and LVEF ≤50%, if a rhythm control strategy fails or is not

desired, and ventricular rates remain rapid despite medical therapy,

2a B-R
atrioventricular nodal ablation with implantation of a CRT device is reasonable .

5. For patients with chronic HF and permanent/persistent/paroxysmal AF, chronic

2a B-NR anticoagulant therapy is reasonable for men and women without additional risk

factors.

165
Special Populations

166
 Disparities and Vulnerable Populations*

Recommendations for Disparities and Vulnerable Populations

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In vulnerable patient populations at risk for health disparities, HF risk

assessments and multidisciplinary management strategies should target both

1 C-LD
known risks for CVD and social determinants of health, as a means toward

elimination of disparate HF outcomes.

2. Evidence of health disparities should be monitored and addressed at the clinical
1 C-LD practice and the health care system levels.

167
 Table 27. Risk of HF and Outcomes in Special Populations

Vulnerable Population Risk of HF HF Outcomes

Women The lifetime risk of HF is equivalent between Overall, more favorable survival with HF than men.
sexes, but HFpEF risk is higher in women—in In the OPTIMIZE-HF registry, women with acute HF
FHS participants with new-onset HF, odds of had a lower 1-y mortality (HR, 0.93; 95% CI, 0.89–
HFpEF (EF >45%) are 2.8-fold higher in women 0.97), although women are more likely not to receive
than in men. optimal GDMT.

Sex-specific differences in the predictive value of Lower patient-reported quality of life for women with
cardiac biomarkers for incident HF. HFrEF, compared with men.

Nontraditional cardiovascular risk factors, Greater transplant waitlist mortality for women but
including anxiety, depression, caregiver stress, equivalent survival after heart transplantation or
and low household income may contribute more LVAD implantation.
toward incident heart disease in women than men.

168
 Table 27. Risk of HF and Outcomes in Special Populations
(con’t.)
Per FHS, at 40 y of age, the lifetime risk Among 1233 patients with HF aged ≥80 y,
Older adults of incident HF is 20% for both sexes; at 40% mortality during mean 27-mo follow-up;
80 y of age, the risk remains 20% for men survival associated with prescription of
and women despite the shorter life GDMT.
expectancy.

LVEF is preserved in at least two-thirds of

older adults with the diagnosis of HF.
Among 27,078 White and Black adults of Age-adjusted 1999–2018 HF mortality
Lower socioeconomic status low income (70% earned <$15,000/y) (deaths/100,000; mean and 95% CI) was
participating from 2002–2009 in the higher with increasing quartiles of ADI,
populations Southern Community Cohort Study, a 1 which is based on 17 indicators of
interquartile increase in neighborhood employment, poverty, and education:
deprivation index was associated with a Quartile 1, 20.0 (19.4–20.5);
12% increase in risk of HF (adjusted HR,
1.12; 95% CI, 1.07–1.18). Quartile 2, 23.3 (22.6–24.0);
Quartile 3, 26.4 (25.5–27.3);
Quartile 4, 33.1 (31.8–34.4) .

169
 Table 27. Risk of HF and Outcomes in Special Populations
(con’t.)
In MESA, patients of Black race had CDC data show race-based differences in HF
Black populations highest risk of incident HF (4.6/1000 mortality over time: Black men had a 1.16-
person-years) and highest proportion of fold versus 1.43-fold higher age-adjusted HF-
nonischemic incident HF. related CVD death rate compared with White
men in 1999 versus 2017; Black women had a
Higher prevalence of HF risk factors 1.35-fold versus 1.54-fold higher age-
including hypertension, obesity, and adjusted HF-related CVD death rate
diabetes, compared with White compared with White women in 1999 versus
populations. 2017.

Gap in outcomes is more pronounced among

younger adults (35–64 y of age) versus older
adults (65–84 y of age); age-adjusted HF-
related CVD death rates were 2.60-fold and
2.97-fold higher in young Black versus White
men and women, respectively.

Higher rates of hospitalization and mortality

among patients with HFpEF.

Lower 5-year survival after heart transplant.

170
 Table 27. Risk of HF and Outcomes in Special Populations
(con’t.)

Hispanic populations MESA study showed higher HF incidence in Despite higher rates of hospitalization for HF
Hispanic compared with non-Hispanic compared with non-Hispanic Whites, Hispanic
White groups (3.5 versus 2.4 per 1000 patients with HF have shown lower short-term
person-years) but lower than for African mortality rates.
Americans (4.6/1000 person-years).
In GWTG, Hispanic patients with HFpEF had
lower mortality (OR, 0.50; 95% CI, 0.31–0.81)
than non-Hispanic Whites, but this was not the
case for Hispanic patients with HFrEF (OR,
0.94; 95% CI, 0.62–1.43).

Lower risk of developing AF in the setting of

HF, compared with White patients.

171
 Table 27. Risk of HF and Outcomes in Special Populations
(con’t.)
Asian and Pacific Islander Limited population-specific data for Asian High rates of preventable HF hospitalization
populations and pacific Islander subgroups in the United observed in some Asian and Pacific Islander
States. populations.
Lower mortality rates from HF for Asian
subgroups when listed as the primary cause of
death, compared with non-Hispanic White
groups.
Native American and Alaskan Native Limited population-specific data, with Limited data suggest HF mortality rates in
populations cardiovascular risk factor trends best American Indians and Alaska Natives are
characterized by the Strong Heart Study and similar to those in White populations.
Strong Heart Family Study, demonstrating
high rates of hypertension and diabetes.
CDC indicates Centers for Disease Control and Prevention; CVD, cardiovascular disease; FHS, Framingham Heart Study; GDMT, guideline-
directed medical therapy; GWTG, Get With The Guidelines registry; HF, heart failure; HFpEF, heart failure with preserved ejection fraction;
HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; LVAD, left ventricular assist device; LVEF, left ventricular ejection
fraction; MESA, Multi-Ethnic Study of Atherosclerosis; OPTMIZE-HF, Organized Program To Initiate Lifesaving Treatment In Hospitalized
Patients With Heart Failure; and OR, odds ratio.

172
 Cardio-Oncology

Recommendations for Cardio-Oncology

Referenced studies that support the recommendations are summarized in the Online Data Supplements.

COR LOE Recommendations

1. In patients who develop cancer therapy–related cardiomyopathy or HF, a

multidisciplinary discussion involving the patient about the risk-benefit ratio of cancer
1 B-NR
therapy interruption, discontinuation, or continuation is recommended to improve

management.
2. In asymptomatic patients with cancer therapy–related cardiomyopathy (EF <50%),

ARB, ACEi, and beta blockers are reasonable to prevent progression to HF and improve
2a B-NR
cardiac function.

173
 Cardio-Oncology (con’t.)
3. In patients with cardiovascular risk factors or known cardiac disease being

considered for potentially cardiotoxic anticancer therapies, pretherapy

2a B-NR
evaluation of cardiac function is reasonable to establish baseline cardiac

function and guide the choice of cancer therapy.

4. In patients with cardiovascular risk factors or known cardiac disease receiving

2a B-NR potentially cardiotoxic anticancer therapies, monitoring of cardiac function is

reasonable for the early identification of drug-induced cardiomyopathy.

5. In patients at risk of cancer therapy–related cardiomyopathy, initiation of beta

2b B-R blockers and ACEi/ARB for the primary prevention of drug-induced

cardiomyopathy is of uncertain benefit.

174
 Cardio-Oncology (con’t.)

6. In patients being considered for potentially cardiotoxic therapies, serial

2b C-LD measurement of cardiac troponin might be reasonable for further risk

stratification.

175
 Table 28. Cancer Therapies Known to Be Associated
With Cardiomyopathy

Cardiac Function

Monitoring Often

Class Agent(s) Performed in Clinical

Practice
Pretherapy Serial
Anthracyclines Doxorubicin, epirubicin X X
Alkylating agents Cyclophosphamide, ifosfamide, melphalan X
Antimicrotubule agents Docetaxel
Antimetabolites Fluorouracil, capecitabine, fludarabine, decitabine
Anti-HER2 agents Trastuzumab, pertuzumab X X
Monoclonal antibodies Rituximab

176
 Table 28. Cancer Therapies Known to Be Associated
With Cardiomyopathy (con’t.)

Dabrafenib, dasatinib, lapatinib, pazopanib, ponatinib,

Tyrosine-kinase inhibitors sorafenib, trametinib, sunitinib, vandetanib, imatinib,

vandetanib
Immune checkpoint inhibitors Nivolumab, ipilimumab, pembrolizumab
Protease inhibitors Bortezomib, carfilzomib
Goserelin, leuprolide, flutamide, bicalutamide,
Endocrine therapy
nilutamide
Chimeric antigen receptor T-cell therapy Tisagenlecleucel, axicabtagene ciloleucel X
Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation X
Radiation Chest

177
Table 29. Risk Factors for Cancer Therapy–Related
Cardiomyopathy

Age ≥60 y
Black race
CAD
Hypertension
Diabetes
Preexisting cardiomyopathy
Previous exposure to anthracyclines
Previous chest radiation
Elevated troponin pretherapy

CAD indicates coronary artery disease.

178
 HF and Pregnancy
Recommendations for HF and Pregnancy

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. In women with a history of HF or cardiomyopathy, including previous peripartum

1 C-LD cardiomyopathy, patient-centered counseling regarding contraception and the risks of

cardiovascular deterioration during pregnancy should be provided.

2. In women with acute HF caused by peripartum cardiomyopathy and LVEF <30%,

2b C-LD anticoagulation may be reasonable at diagnosis, until 6 to 8 weeks postpartum,

although the efficacy and safety are uncertain.

3. In women with HF or cardiomyopathy who are pregnant or currently planning for

3: Harm C-LD pregnancy, ACEi, ARB, ARNi, MRA, SGLT2i, ivabradine, and vericiguat should not

be administered because of significant risks of fetal harm.

179
 Table 30. HF Management Strategies Across the
Pregnancy Continuum
Preconception During Pregnancy Postpartum
Nonpharmacological strategies Preconception genetic counseling Close maternal monitoring for HF signs or Multidisciplinary recommendations from
and testing for potentially heritable symptoms or other cardiovascular instability by obstetrics and neonatology and pediatrics
cardiac conditions. cardiology and obstetric and maternal-fetal teams and shared decision-making
medicine teams; close fetal monitoring by the regarding the maternal and neonatal risks
Use of pregnancy cardiovascular obstetric and maternal-fetal medicine teams. and benefits of breastfeeding.
risk tools, and echocardiography for
myocardial structure and function Consideration of routine echocardiographic For women presenting with
assessment, to provide information screening in the third trimester for reassessment decompensated HF or cardiogenic shock,
that facilitates informed counseling. of myocardial structure and function before HF management should include
labor; echocardiography for any significant hemodynamic monitoring and mechanical
For women planning a pregnancy, changes in HF symptoms or signs during circulatory support as appropriate
provide personalized counseling that pregnancy, or if HF medications are reduced or
promotes the autonomy and goals of discontinued.
the patient (and her partner, as
applicable), the patient’s ability for BNP or NT-proBNP monitoring during
self-care and risk awareness, and pregnancy may have some value for prediction
ensures adequate psychosocial of cardiovascular events.
support for decision-making.
Close maternal monitoring by obstetrics and
For women not currently planning a maternal-fetal medicine teams for preeclampsia,
pregnancy but who might conceive, which has shared risk factors and pathogenesis
discuss HF-specific considerations with PPCM.
regarding pregnancy and refer to
gynecology or primary care for For women presenting with decompensated HF
contraceptive counseling. or cardiogenic shock, hemodynamic monitoring
and MCS, as appropriate, within a
multidisciplinary collaborative approach that
supports prompt decision-making about the
timing and mechanism of delivery.

180
 Table 30. HF Management Strategies Across the
Pregnancy Continuum (con’t.)
Pharmacological strategies Review of all current medications. Close monitoring of maternal blood pressure, heart rate, For women with acute HF caused by PPCM and
For women planning pregnancy and volume status, with adjustment of the modified HF LVEF <30%, consideration of anticoagulation
imminently, modification of HF regimen as appropriate to avoid hypotension (systemic until 6–8 wk postpartum, although the efficacy
pharmacotherapy including. vasodilation peaks in the second trimester) and and safety remain uncertain at this time.
discontinuation of any ACEi, ARB, placental hypoperfusion. For postpartum women with severe acute HF
ARNi, MRA, or SGLT2i or ivabradine For women with HF or cardiomyopathy presenting caused by PPCM and LVEF <35%, in GDMT
medications; within a construct of during pregnancy without preconception counseling and pharmacotherapy and prophylactic
multidisciplinary shared decision-making, assessment, urgent discontinuation of any GDMT anticoagulation, to improve LVEF recovery; the
continuation of a beta blocker (most pharmacotherapies with fetal toxicities; within a efficacy and safety of bromocriptine for acute
commonly metoprolol), hydralazine, and construct of multidisciplinary shared decision-making, PPCM treatment remains uncertain at this time,
nitrates; adjustment of diuretic dosing to continuation of a beta blocker (most commonly particularly in the setting of contemporary HF
minimize the risk of placental metoprolol succinate), hydralazine, and nitrates; GDMT and cardiogenic shock management.*
hypoperfusion. adjustment of diuretic dosing to minimize the risk of
Ideally, repeat echocardiography placental hypoperfusion. For women who choose to breastfeed, review
approximately 3 mo after preconception medications with neonatology and pediatrics
HF medication adjustments to ensure teams for neonatal safety during lactation,
stability of myocardial structure and ideally with pharmacist consultation if available.
function before conception. Within a construct of multidisciplinary shared
decision-making, medications that may be
appropriate during breastfeeding include ACEi
(enalapril or captopril preferred, monitor
neonatal weight), beta blockers (metoprolol
preferred, monitor neonatal heart rate).
Diuretics can suppress lactation, but with
neonatal follow-up the use of furosemide may be
appropriate.

181
 Table 30. HF Management Strategies Across the
Pregnancy Continuum (con’t.)
Multidisciplinary care beyond the Consultation with genetics, Multidisciplinary management with obstetrics Multidisciplinary management with
cardiology team gynecology, and maternal-fetal and maternal-fetal medicine teams during obstetrics, maternal-fetal medicine,
medicine teams, as appropriate to pregnancy. neonatology, and pediatrics teams,
the outcome of shared decision- For women with decompensated HF or evidence especially for multidisciplinary
making. of hemodynamic instability antepartum, delivery recommendations regarding lactation.
planning will include obstetrics and maternal- Consultation with gynecology team for
fetal medicine, anesthesia, and neonatology ongoing contraceptive planning.
teams.

ACEi indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi,
angiotensin receptor-neprilysin inhibitor; BNP, B-natriuretic peptide; GDMT, guideline-directed
medical therapy; HF, heart failure; LVEF, left ventricular ejection fraction; MCS, mechanical
circulatory support; MRA, mineralocorticoid receptor antagonist; NT-proBNP, N-terminal
prohormone of brain natriuretic peptide; PPCM, peripartum cardiomyopathy; RCT, randomized
controlled trial; RV, right ventricular; and SGLT2i, sodium-glucose cotransporter-2 inhibitor.

182
Quality Metrics and Reporting

183
 Quality Metrics and Reporting

Recommendations for Performance Measurement

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations

1. Performance measures based on professionally developed clinical practice

1 B-NR guidelines should be used with the goal of improving quality of care for

patients with HF.

2. Participation in quality improvement programs, including patient registries

that provide benchmark feedback on nationally endorsed, clinical practice

2a B-NR
guideline–based quality and performance measures can be beneficial in

improving the quality of care for patients with HF.

184
 Table 31. ACC/AHA 2020 HF Clinical Performance,
Quality, and Structural Measures
Measure
Measure No. Measure Title Care Setting Attribution Domain
PM-1 LVEF assessment Outpatient Individual Diagnostic
practitioner
Facility
PM-2 Symptom and activity assessment Outpatient Individual Monitoring
practitioner
Facility
PM-3 Symptom management Outpatient Individual Treatment
practitioner
Facility
PM-4 Beta-blocker therapy for HFrEF Outpatient Individual Treatment
Inpatient practitioner
Facility
PM-5 ACEi, ARB, or ARNi therapy for HFrEF Outpatient Individual Treatment
Inpatient practitioner
Facility
PM-6 ARNi therapy for HFrEF Outpatient Individual Treatment
Inpatient practitioner
Facility

185
 Table 31. ACC/AHA 2020 HF Clinical Performance,
Quality, and Structural Measures (con’t.)
PM-7 Dose of beta blocker therapy for HFrEF Outpatient Individual Treatment
practitioner
Facility
PM-8 Dose of ACEi, ARB, or ARNi therapy for HFrEF Outpatient Individual Treatment
practitioner
Facility
PM-9 MRA therapy for HFrEF Outpatient Individual Treatment
Inpatient practitioner
Facility
PM-10 Laboratory monitoring in new MRA therapy Outpatient Individual Monitoring
Inpatient practitioner
Facility
PM-11 Hydralazine and isosorbide dinitrate therapy for HFrEF Outpatient Individual Treatment
in those patients self-identified as Black or African Inpatient practitioner
American Facility
PM-12 Counseling regarding ICD placement for patients with Outpatient Individual Treatment
HFrEF on GDMT practitioner
Facility

186
 Table 31. ACC/AHA 2020 HF Clinical Performance,
Quality, and Structural Measures (con’t.)

PM-13 CRT implantation for patients with HFrEF on GDMT Outpatient Individual Treatment
practitioner
Facility
QM-1 Patient self-care education Outpatient Individual Self-Care
practitioner
Facility
QM-2 Measurement of patient-reported outcome-health status Outpatient Individual Monitoring
practitioner
Facility
QM-3 Sustained or improved health status in HF Outpatient Individual Outcome
practitioner
Facility
QM-4 Post-discharge appointment for patients with HF Inpatient Individual Treatment
practitioner, facility
SM-1 HF registry participation Outpatient Facility Structure
Inpatient

187
 Table 31. ACC/AHA 2020 HF Clinical Performance,
Quality, and Structural Measures (con’t.)

Rehabilitation PMs Related to HF (From the 2018 ACC/AHA performance measures for cardiac rehabilitation (10))
Exercise training referral for HF from inpatient
Rehab PM-2 setting Inpatient Facility Process

Individual
Exercise training referral for HF from outpatient practitioner
Rehab PM-4 setting Outpatient Facility Process

ACEi indicates angiotensin-converting enzyme inhibitor; ACC, American College of Cardiology;

AHA, American Heart Association; ARB, angiotensin receptor blocker; ARNi, angiotensin
receptor-neprilysin inhibitor; CRT, cardiac resynchronization therapy; GDMT, guideline-directed
medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ICD,
implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; MRA,
mineralocorticoid receptor antagonist; PM, performance measure; QM, quality measure; and
SM, structural measure.

188
Goals of Care

189
 Palliative and Supportive Care, Shared
Decision-Making, and End-of-Life
Recommendations for Palliative and Supportive Care, Shared Decision-Making, and End-of-Life

Referenced studies that support the recommendations are summarized in the Online Data Supplements.
COR LOE Recommendations
1. For all patients with HF, palliative and supportive care—including high-quality

communication, conveyance of prognosis, clarifying goals of care, shared decision-

1 C-LD
making, symptom management, and caregiver support—should be provided to

improve QOL and relieve suffering.

2. For patients with HF being considered for, or treated with, life-extending therapies,

the option for discontinuation should be anticipated and discussed through the
1 C-LD
continuum of care, including at the time of initiation, and reassessed with changing

medical conditions and shifting goals of care.

190
 Palliative and Supportive Care, Shared
Decision-Making, and End-of-Life (con’t.)
3. For patients with HF—particularly stage D HF patients being evaluated for

advanced therapies, patients requiring inotropic support or temporary

mechanical support, patients experiencing uncontrolled symptoms, major

2a B-R
medical decisions, or multimorbidity, frailty, and cognitive impairment—

specialist palliative care consultation can be useful to improve QOL and relieve

suffering.
4. For patients with HF, execution of advance care directives can be useful to

2a C-LD improve documentation of treatment preferences, delivery of patient-centered

care, and dying in preferred place.

5. In patients with advanced HF with expected survival <6 months, timely referral
2a C-LD
to hospice can be useful to improve QOL.
191
 Table 32. Palliative and Supportive Care Domains to
Improve Processes of Care and Patient Outcomes

Palliative and Supportive Domains of What Palliative Care Adds to Overall HF Management
Care
High-quality communication Central to palliative care approaches are communication and patient-caregiver
engagement techniques.
Conveyance of prognosis Palliative care specifically addresses patient and caregiver understanding of disease,
treatment, and prognosis. Research suggests that patients tend to overestimate their
survival and overestimate the potential benefits of treatment. Objective risk models can
calibrate expectations, but discussion of uncertainty should accompany prognostic
conversations, often summarized as “hope for the best, plan for the worst.”
Clarifying goals of care Management of patients with HF as their disease becomes end-stage and death seems
near includes decisions about when to discontinue treatments designed primarily to
prolong life (e.g., ICD, hospitalization, tube feeding), decisions on when to initiate
treatments to reduce pain and suffering that may hasten death (e.g., narcotics), and
decisions about the location of death, home services, and hospice care. Exploring
patients’ expressed preferences, values, needs, concerns, means and desires through
clinician-led discussion can clarify values-treatment concordance and improve medical
decision-making.

192
 Table 32. Palliative and Supportive Care Domains to
Improve Processes of Care and Patient Outcomes
Shared decision-making is a process by which patients and clinicians work together to
Shared decision-making make optimal health care decisions from medically reasonable options that align with
what matters most to patients. Shared decision-making requires: unbiased medical
evidence about the risks, benefits, and burdens of each alternative, including no
intervention; clinician expertise in communication and tailoring that evidence for
individual patients; and patient goals and informed preferences.

Dyspnea, fatigue, pain, nausea, depression, anxiety, and other symptoms of HF

Symptom management refractory to cardiovascular therapies can be partially remediated through palliative and
supportive approaches in addition to GDMT.

Care of the patient with heart failure should extend to their loved ones, including
Caregiver support beyond their death, to offer support to families and help them cope with loss.

GDMT indicates guideline-directed medical therapy; HF, heart failure; and ICD, implantable
cardioverter-defibrillator.

193
Figure 15. A
Depiction of
the Clinical
Course of HF
With
Associated
Types and
Intensities of
Available
Therapies
Over Time
CHF indicates congestive
heart failure; HF, heart
failure; and MCS,
mechanical circulatory
support.

194
 Recommendation for Patient-
Reported Outcomes and Evidence
Gaps and Future Research Directions

195
 Patient-Reported Outcomes

Recommendation for Patient-Reported Outcomes

COR LOE Recommendation

1. In patients with HF, standardized assessment of patient-reported health status

using a validated questionnaire can be useful to provide incremental

2a C-LD
information for patient functional status, symptom burden, and prognosis.

196
 Table 33. Evidence Gaps and Future Research Directions

Definition
• Consensus on specific classifications of HFrEF, HFpEF, HFmrEF, and HFimpEF or whether a 2-category definition of HFrEF and

HF with normal EF, or an additional category of HFimpEF is needed separately for HFpEF; and whether these approaches can be

uniformly applied to clinical trials and practice.

• Definitions, detection, and management of myocarditis and myocardial injury, especially in the context of rapidly evolving

concepts, such as COVID-19 infection and cardiotoxicity.

• Definition and classification of cardiomyopathies.
Screening
• Cost-effectiveness of different strategies to screen for HF.
• Prediction of higher risk for HF among patients with traditional risk factors (e.g., which patients with diabetes would be at a higher

risk HF, warranting preventive treatment for HF).

197
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)
Diagnostics and Monitoring
• Individualized treatment targeting specific causes.
• Advanced role of precision medicine with incorporation of genetic, personalized, and individualized factors in medical management

of HF.
• High-value methods to use biomarkers in the optimization of medical therapy.
• Ability to use integrated systems biology models, including biomarkers, molecular markers, omics, diagnostic modalities, and

genetic variables for diagnosis, prognosis, and targeting therapies.

• Ability to monitor and adjust therapy to individual changes over time.
Nonmedical Strategies
• Efficacy and safety of specific dietary interventions, sodium restriction, and fluid restriction to prevent and treat HF.
• Efficacy and safety of cardiac rehabilitation in patients with HFpEF and HFmrEF.

198
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)

Medical Therapies
• Effective management strategies for patients with HFpEF.
• Evidence for specific treatment strategies for HFmrEF.
• Research on causes and targeted therapies for cardiomyopathies such as peripartum cardiomyopathy.
• Treatment of asymptomatic LV dysfunction to prevent transition to symptomatic HF.
• Therapies targeting different phenotypes of HF; patients with advanced HF, persistent congestion, patients with profiles excluded

from clinical trials such as those with advanced kidney failure or hypotension.
• Studies on targets for optimal decongestion; treatment and prevention of cardiorenal syndrome and diuretic resistance.
• Diagnostic and management strategies of RV failure.
• Efficacy and safety of hydralazine isosorbide in non–African American patients with HF and also in African American patients on

GDMT including SGLT2i and ARNi.

• Efficacy and safety of vericiguat in patients with HFrEF and markedly elevated natriuretic peptide levels.

199
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)

• Efficacy and safety of omecamtiv mecarbil in patients with stage D (advanced HF) HFrEF.
• Additional efficacy and safety of SGLT2i therapies in patients with HFpEF or patients with HFmrEF, efficacy and safety of

combined SGLT2i and SGLT1i in HFrEF, HFmrEF, or HFpEF.

• Additional efficacy and safety of SGLT2i studies in hospitalized patients with acute decompensated HF with and without diabetes.
• Efficacy and safety of nonsteroidal, selective MRA in patients with HF.
• Efficacy and safety of ARNi in pre-HF stage (stage B).
• Effective management strategies for combined post- and precapillary pulmonary hypertension.
• Novel treatments for ATTR cardiomyopathy.
• Treatment strategies targeting downstream processes such as fibrosis, cardiac metabolism or contractile performance in dilated

cardiomyopathies and HFpEF.

• Comparative effectiveness and safety of different initiation and titration of GDMT at the same time or in different sequences,

optimal strategies for sequencing and titration of therapies for HFrEF and HFpEF.

200
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)

• Studies on prediction of patient response; studies on how to incorporate patient preferences.

• Efficacy and safety of optimal BP target in patients with established HF and hypertension.
• Optimal BP target while optimizing GDMT in patients with HFrEF and HFpEF.
• Appropriate management of electrolyte abnormalities in HF (e.g., hyperkalemia or hypokalemia).
• Role of potassium binders in optimization of GDMT and clinical outcomes in patients with HF.
• Efficacy and safety of pirfenidone and other targeted treatment strategies for maladaptive fibrosis in patients with HFpEF.
• AF risk in patients treated with PUFA for patients at risk for HF or with HF.
Device Management and Advanced Therapies
• Optimal and timely selection of candidates for percutaneous interventions, MCS, or cardiac transplantation.
• Interventional approaches to recurrent, life-threatening ventricular tachyarrhythmias.
• Comparative effectiveness of His-bundle pacing or multisite pacing to prevent progression of HF.

201
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)

• Safety and efficacy of cardiac contractility modulation, vagal nerve stimulation, autonomic modulation, and renal denervation in

patients with HF.

• Safety and efficacy of splanchnic nerve ablation splanchnic nerve ablation to reduce splanchnic vasoconstriction and volume

redistribution in HF.
• Safety and efficacy of interatrial shunt, pericardiectomy, baroreceptor and neuromodulation, and renal denervation in HFpEF.
• Safety and efficacy of percutaneous or surgical interventions for tricuspid regurgitation.
Clinical Outcomes
• Impact of therapies in patient-reported outcomes, including symptoms and QOL.
• Studies addressing patient goals about care and care intensity as it intersects with disease trajectory.
• Real-world evidence data to characterize generalization of therapies in HF populations who may not have been represented in trials.

202
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)
Systems of Care and Social Determinants of Health
• Implementation studies on how to develop a structured approach to patient participation in informed decision-making and goal

setting through the continuum of HF care.

• Implementation science for adoption and optimization of GDMT by clinicians on how to initiate multiple or sequenced GDMT, how

to integrate these into learning health systems and networks, and how to increase patient education and adherence.
• Pragmatic studies on multidisciplinary new care models (e.g., cardiac teams for structural and valve management, shock teams,

cardiometabolic clinics, telemedicine, digital health, cardiac rehabilitation at home or postdischarge, and palliative care).
• Studies on strategies to eliminate structural racism, disparities, and health inequities in HF care.
• Studies addressing evidence gaps in women, racial, and ethnic populations.
• Management strategies for palliative care.
• Identification of factors that lead to unwarranted variations in HF care.
• Identify characteristics of systems of care (e.g., disciplines and staffing, electronic health records, and models of care) that optimize

GDMT before and after the discharge of hospitalized patients.

203
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)

Comorbidities
• Further studies on rhythm control versus ablation in AF.
• Appropriate patient selection in evolving percutaneous approaches in VHD (e.g., timing and appropriate patient selection for TAVI,

Mitraclip, tricuspid valve interventions).

• Effective and safe treatment options in CKD, sleep-disordered breathing, chronic lung disease, diabetes, depression, cognitive

disorders, and iron deficiency.

• Efficacy and safety of transvenous stimulation of the phrenic nerve or role of nocturnal supplemental oxygen for treatment of

central sleep apnea in patients with HF.

• Efficacy and safety of weight loss management and treatment strategies in patients with HF and obesity.
• Efficacy and safety of nutritional and food supplementation in patients with HF and frailty and malnutrition.
• Efficacy and safety of GDMT in end-stage renal disease or in patients with eGFR <30 mL/min/1.73 m2.

204
 Table 33. Evidence Gaps and Future Research Directions
(con’t.)

Future/Novel Strategies
• Pharmacological therapies targeting novel pathways and endophenotypes.
• New device therapies, including percutaneous and durable mechanical support devices.
• Invasive (e.g., pulmonary artery pressure monitoring catheter) or noninvasive remote monitoring.
• Studies on telehealth, digital health, apps, wearables technology, and artificial intelligence.
• Role of enrichment trials, adaptive trials, umbrella trials, basket trials, and machine learning–based trials.
• Therapies targeting multiple cardiovascular, cardiometabolic, renovascular, and pathobiological mechanisms.
• Novel dissemination and implementation techniques to identify patients with HF (e.g., natural language processing of electronic

health records and automated analysis of cardiac imaging data) and to test and monitor proven interventions.
AF indicates atrial fibrillation; ARNi, angiotensin receptor-neprilysin inhibitor; ATTR, transthyretin amyloidosis; BP, blood pressure; CKD, chronic kidney disease;
COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; GDMT, guideline-directed medical therapy; HF, heart failure; HFimpEF, heart
failure with improved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF,
heart failure with reduced ejection fraction; LV, left ventricular; MCS, mechanical circulatory support; MRA, mineralocorticoid receptor antagonist; PUFA,
polyunsaturated fatty acid; QOL, quality of life; RV, right ventricular; SGLT1i, sodium-glucose cotransporter-1 inhibitors; SGLT2i, sodium-glucose
cotransporter-2 inhibitors; TAVI, transcatheter aortic valve implantation; and VHD, valvular heart disease.

205
 Abbreviations

Abbreviation Meaning/Phrase

ACEi angiotensin-converting enzyme inhibitor

ACS acute coronary syndrome

ARNi angiotensin receptor-neprilysin inhibitor

ARB angiotensin (II) receptor blocker

AF atrial fibrillation

AL-CM immunoglobulin light chain amyloid

cardiomyopathy
ATTR-CM transthyretin amyloid cardiomyopathy
ATTRv variant transthyretin amyloidosis
ATTRwt wild-type transthyretin amyloidosis

206
 Abbreviations
BNP B-type natriuretic peptide
CABG coronary artery bypass graft
CAD coronary artery disease
CCM cardiac contractility modulation
CHF congestive heart failure
CKD chronic kidney disease
CMR cardiovascular magnetic resonance
COVID-19 coronavirus disease 2019
CPET cardiopulmonary exercise test
CRT cardiac resynchronization therapy
CRT-D cardiac resynchronization therapy with defibrillation
CRT-P cardiac resynchronization therapy with pacemaker
CT computed tomography
CVD cardiovascular disease
CVP central venous pressure
207
 Abbreviations
DOAC direct-acting oral anticoagulants
DPP-4 dipeptidyl peptidase-4
ECG electrocardiogram
EF ejection fraction
eGFR estimated glomerular filtration rate
FDA U.S. Food and Drug Administration
FLC free light chain
GDMT guideline-directed medical therapy
HF heart failure
HFimpEF heart failure with improved ejection fraction
HFmrEF heart failure with mildly reduced ejection fraction
HFpEF heart failure with preserved ejection fraction
HFrEF heart failure with reduced ejection fraction
ICD implantable cardioverter-defibrillator

208
 Abbreviations

IFE immunofixation electrophoresis

LBBB left bundle branch block

LV left ventricular

LVAD left ventricular assist device

LVEDV left ventricular end-diastolic volume

LVEF left ventricular ejection fraction

LVH left ventricular hypertrophy

MCS mechanical circulatory support

MI myocardial infarction

MR mitral regurgitation

MRA mineralocorticoid receptor antagonist

MV mitral valve

NSAID nonsteroidal anti-inflammatory drug

209
 Abbreviations
NSVT nonsustained ventricular tachycardia

NT-proBNP N-terminal prohormone of B-type natriuretic peptide

NYHA New York Heart Association

QALY quality-adjusted life year

QOL quality of life

PA pulmonary artery

PCWP pulmonary capillary wedge pressure

PET positron emission tomography

PPAR-γ peroxisome proliferator-activated receptor gamma

PUFA polyunsaturated fatty acid

RA right atrial

RAASi renin-angiotensin-aldosterone system inhibitor

RCT randomized controlled trial

RV right ventricular

210
 Abbreviations

SCD sudden cardiac death

SGLT2i sodium-glucose cotransporter-2 inhibitors

SPECT single photon emission CT

99mTc-PYP technetium pyrophosphate

TEE transesophageal echocardiogram

TEER transcatheter mitral edge-to-edge repair

TTE transthoracic echocardiogram

VA ventricular arrhythmia

VF ventricular fibrillation

VHD valvular heart disease

VO2 oxygen consumption/oxygen uptake

VT ventricular tachycardia

211