Heart Failure Pharmacotherapy

Based on the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure More clinical pearls at pyrls.com
References:
[1] Classes of Heart Failure. American Heart Association. May 31, 2017. https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure
[2] Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart
Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033]. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063

Heart Failure Categories Goals of Therapy

Stage A
Stage LVEF NYHA Class • Primary prevention of heart failure

At risk for HF Stage B

A • No HF signs/symptoms
• No structural/functional heart disease
• No abnormal biomarkers
HFrEF
(reduced EF)
LVEF ≤ 40% I • No symptoms from
ordinary daily activities
• Prevention of clinical heart failure

Stage C
Pre-HF
• No HF signs/symptoms LVEF > 40%
II
• No symptom at rest
• ONE of the following:
HFimpEF (upon follow up after a • Ordinary daily physical
• Reduction of mortality

B
(1) Structural heart disease previous measurement of
(2) ↑ filling pressures (improved EF) activities cause HF symptoms • Reduction of heart failure symptoms and
LVEF ≤ 40% )
(3) Risk factors PLUS ↑ natriuretic
peptides OR persistently ↑ cardiac hospitalization risk
troponin w/o competing diagnosis
• Elimination of potential barriers to self-care
LVEF 41-49% • No symptom at rest
HFmrEF (w/ evidence of
spontaneous/provokable III • Activities lighter than
ordinary daily physical Stage D

C
Symptomatic HF
(mildly reduced EF) activities cause HF symptoms
• Structural heart disease AND ↑ LV filling pressures)
• Current or previous HF symptoms
• Provision of inotropic support until mechanical
circulatory support or cardiac
LVEF ≥ 50% transplantation is available

IV
• Symptoms at rest
Advanced HF
HFpEF
D
(w/ evidence of
• HF symptoms interfering with • Discomfort worsens with • Palliative symptom control and functional
normal activity and/or recurrent HF spontaneous/provokable
(preserved EF) physical activities
hospitalizations (despite GDMT) ↑ LV filling pressures) improvement (if not eligible for mechanical
circulatory support or cardiac transplantation)

Pharmacotherapy Recommendations

Stage A Stage B Stage C (HFpEF) Stage C (HFmrEF) Stage C (HFimpEF)

• Control BP in patients with • ACEi and evidence-based • Diuretics as needed • PRN diuretics (loop preferred) • Continue GDMT
hypertension BB in patients with LVEF ≤ 40% (loop preferred) ⚬ Even if asymptomatic
⚬ If LVEF ≤ 40% and recent MI, • SGLT2i may be beneficial
• SGLT2i in patients with use ARB if ACEi is not • SGLT2i may be beneficial
T2DM plus: • May consider MRA, ACEi/ARB/
tolerated ARNi, and evidence-based BB
⚬ Established CVD or, • May consider MRA, ARB/ARNi
⚬ High CV risk if LVEF is closer to 50% particularly if LVEF is closer to -
- - -HFrEF threshold
• Manage existing comorbidities

Stage C (HFrEF) Selected Medications That May Cause or Exacerbate HF

COX inhibitors • ↑ H2O retention, ↑ vascular resistance, ↓ response to diuretics

All patients Specific patients (e.g., NSAIDs) • Immediate onset, major induction/precipitation of HF

Thiazolidinediones • Potential blockage of calcium channel

• Intermediate onset, major induction/precipitation of HF
• ARNi or ACEi or ARB • Hydralazine + isosorbide dinitrate
⚬ ARNi: NYHA class II-III ⚬ African American patients on optimal therapy Saxagliptin, • Mechanism is unclear
⚬ ACEi or ARB: NYHA class II-IV ⚬ NYHA class III-IV Alogliptin • Immediate or delayed onset, major induction/precipitation of HF
⚬ Order of preference: ARNi > ACEi > ARB • Ivabradine
⚬ NYHA class II-IV and LVEF ≤ 35% Flecainide, • Proarrhythmic, negative inotropic effects
⚬ 36-hour washout required when switching Disopyramide • Immediate to intermediate onset, major induction/precipitation of HF
between ACEi and ARNi (and vice versa) ⚬ On GDMT including max tolerated BB
⚬ NSR with resting HR ≥ 70 BPM • Proarrhythmic effects, beta blockade
Sotalol
• Beta Blocker (evidence-based) • Vericiguat • Immediate to intermediate onset, major induction/precipitation of HF
⚬ Bisoprolol, carvedilol, metoprolol succinate ⚬ NYHA class II-IV and LVEF < 45%
• Negative inotropic effects
⚬ Recent HF worsening Dronedarone
• Immediate to intermediate onset, major induction/precipitation of HF
⚬ ↑ BNP or NT-proBNP
• MRA (e.g. eplerenone, spironolactone)
⚬ NYHA class II-IV • Digoxin • Beta-1 stimulation, ↑ renin and aldosterone
Doxazosin
⚬ If symptomatic despite GDMT or • Intermediate to delayed onset, moderate induction/precipitation of HF
⚬ eGFR > 30 mL/min/1.73m2
⚬ Unable to tolerate GDMT
⚬ Serum potassium < 5 mEq/L Diltiazem, • Negative inotropic effects
• Potassium binders Verapamil • Immediate to intermediate onset, major induction/precipitation of HF
⚬ e.g., Patiromer, sodium zirconium cyclosilicate
• SGLT2i
⚬ Patients with hyperkalemia (K+ ≥ 5.5 mEq/L) • Negative inotropic effects
⚬ With or without T2DM Nifedipine • Immediate to intermediate onset, moderate induction/precipitation
while on RAASi
of HF
• Omega-3 PUFA (may consider as an adjunct)
• Diuretics (as needed)
⚬ NYHA class II-IV
⚬ Loop diuretics preferred Recreated from Table 13 from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

ACEi: angiotensin-converting enzyme inhibitors
ARB: angiotensin (II) receptor blocker
ARNi: angiotensin receptor-neprilysin inhibitors
BB: beta-blocker
BNP: B-type natriuretic peptide
BP: blood pressure
CVD: cardiovascular disease
eGFR: estimated glomerular filtration rate
GDMT: guideline-directed medical therapy
HF: heart failure
Abbreviations
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
LVEF: left ventricular ejection fraction PRN: as needed
MI: myocardial infarction PUFA: polyunsaturated fatty acid
MRA: mineralocorticoid receptor antagonist RAASi: renin-angiotensin-aldosterone system inhibitor
NT-proBNP: N-terminal prohormone of B-type natriuretic peptide SGLT2i: sodium-glucose cotransporter-2 inhibitor
NYHA: New York Heart Association T2DM: type 2 diabetes mellitus

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