Congestive heart failure pharmacotherapy

Congestive Heart Failure Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Cardiac MRI

Echocardiography

Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies

Treatment

Invasive Hemodynamic Monitoring

Medical Therapy:

Summary

Acute Pharmacotherapy

Chronic Pharmacotherapy in HFpEF

Chronic Pharmacotherapy in HFrEF

Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
Hydralazine
Positive Inotropics
Anticoagulants
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure pharmacotherapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Congestive heart failure pharmacotherapy

CDC on Congestive heart failure pharmacotherapy

Congestive heart failure pharmacotherapy in the news

Blogs on Congestive heart failure pharmacotherapy

Directions to Hospitals Treating Congestive heart failure pharmacotherapy

Risk calculators and risk factors for Congestive heart failure pharmacotherapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief:  Sara Zand, M.D.[2] Seyedmahdi Pahlavani, M.D. [3]

## Overview

[edit | edit source]

Management of heart failure is guided by ejection fraction phenotype (HFrEF vs HFmrEF/HFpEF), clinical stage, congestion status, and underlying etiology, with the goals of improving symptoms, reducing hospitalization, and improving survival. Contemporary care prioritizes rapid initiation and optimization of GDMT (foundational 4-drug therapy in HFrEF; SGLT2 inhibitor–centered, comorbidity-driven therapy with selective ARNI/ARB/MRA in HFmrEF/HFpEF) alongside diuretics for relief of congestion. Longitudinal management requires structured reassessment of symptoms, vitals, renal function/electrolytes, and cardiac function to guide titration, add-on therapies, and candidacy for ICD/CRT or structural interventions, with referral for advanced HF therapies when progression occurs. Effective implementation is strengthened by multidisciplinary HF programs, patient education and lifestyle interventions, and coordinated transitions of care.

## Management of patients with heart failure with reduced ejection fraction (HFrEF)

[edit | edit source]

The 2022 AHA/ACC/HFSA approach to chronic stage C HFrEF (LVEF ≤40%) emphasizes early initiation of the 4 pillars of guideline-directed medical therapy (GDMT), including ARNi (preferred) or ACEi/ARB, an evidence-based beta-blocker, a MRA in eligible patients, and an SGLT2 inhibitor, alongside diuretics for relief of congestion, with subsequent dose uptitration to target as tolerated. In parallel, patients should be evaluated for device and interventional therapies (e.g., ICD/CRT in appropriate candidates) and referred to an HF specialty team if progressing to advanced/refractory symptoms despite optimized GDMT.

| Stage C HFrEF
(LVEF ≤40%)|

|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|

| Initial Assessment
• Assess congestion/hemodynamics
• Fluid overloaded → Diuretics (Class I)|

| Initiate Foundational GDMT (Class I)
• ARNi / ACEi / ARB
• Beta-Blocker
• MRA
• SGLT2i|

| Titrate GDMT to Target/Max Tolerated Dose
• Monitor labs & vitals
• Reassess Symptoms & LVEF|

| LVEF >40%
HFimpEF
Continue GDMT|

| LVEF ≤40%
Persistent HFrEF|

| Additional Therapies
• African American + NYHA III-IV → Hydralazine-Nitrates
• NYHA I-III + LVEF ≤35% + Survival >1 yr → ICD
• NYHA II-III + LVEF ≤35% + NSR + LBBB + QRS ≥150 ms → CRT-D
• Consider: Ivabradine, Vericiguat, IV Iron|

| Reassess Symptoms & Status|

| Symptoms Improved
Continue GDMT|

| Refractory HF
(Stage D)

| Advanced HF Management
• HF Specialty Referral
• Durable MCS / LVAD
• Cardiac Transplant
• Palliative Care

ARNi: Angiotensin Receptor-Neprilysin inhibitor; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin II Receptor Blocker; MRA: Mineralocorticoid Receptor Antagonist; SGLT2i: Sodium Glucose Cotransporter 2 inhibitors; ICD: Implantable Cardioverter-Defibrillator; CRT-D: Cardiac Resynchronization Therapy with Defibrillator; CRT-P: Cardiac Resynchronization Therapy with Pacemaker; MCS: Mechanical Circulatory Support; LVAD: Left Ventricular Assist Device

The above algorithm is adopted from 2022 AHA/ACC/HFSA Guidelines for Management of Heart Failure[1]

### Treatment Algorithm for Guideline-Directed Medical Therapy Including Novel Therapies

[edit | edit source]

| Heart failure  reduced EF, stage C, treatment|

|
|
|
|
|
|
|
|
|
|
|
|
|
|

| ARNI, ACEI, ARB|

| For patients with eGFR≥ 30 mL/min/1.73m² or creatinine≤ 2.5 mg/dL in males or ≤2 mg/dL in females or K≤ 5 mEq/L, NYHA 2-4|

| For patients with eGFR criteria, NYHA 2-4|

| For patients with persistent volume overload, NYHA 2-4|

| For symptomatic black patients despite receiving ARNI, betablocker,aldosterone antagonist, SGLT2 inhibitor, NYHA 3-4|

| For patients with resting HR>70/min despite maximum tolerated betablocker dose, sinus rhythm, NYHA 2-3

| Add|

| Add|

| Titrate|

| Add|

| Add|

| Aldosterone antagonist|

| SGLT2 inhibitor|

| Diuretic agents|

| Hydralazine \+ Isosorbide dinitrate|

| Ivabradine|

ARNi: Angiotensin Receptor-Neprilysin inhibitor; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin II Receptor Blocker; SGLT2i: Sodium Glucose Cotransporter 2 inhibitors

The above algorithm is adopted from 2021 AHA/ACC Guideline[2]

## Management of patients with heart failure with preserved ejection fraction (HFrEF)

[edit | edit source]

HFpEF management in the 2022 AHA/ACC/HFSA framework recommends optimizing comorbidities (especially hypertension), using diuretics for congestion, initiating an SGLT2 inhibitor to reduce HF hospitalizations and CV mortality, and selectively adding MRAs, ARBs, or ARNI to reduce hospitalizations, particularly when LVEF is at the lower end of the preserved range.

| Symptomatic HF
LVEF ≥50%|

|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|

| Diuretics,
as needed
(Class I)|

| SGLT2i
(Class IIa)|

| ARNi*
(Class IIb)|

| MRA*
(Class IIb)|

| ARB*
(Class IIb)|

*Greater benefit in patients with LVEF closer to 50%.

ARNi: Angiotensin Receptor-Neprilysin inhibitor; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin II Receptor Blocker; MRA: Mineralocorticoid Receptor Antagonist; SGLT2i: Sodium Glucose Cotransporter 2 inhibitors

The above algorithm is adopted from 2022 AHA/ACC/HFSA Guidelines for Management of Heart Failure[1]

## Congestive heart failure treatment summary based on 2021 AHA/ACC Guideline[2]

[edit | edit source]

Pathophysiology  | Treatment

|

Renin-angiotensin-aldosterone system | ARNIs/ACEIs/ARBs, aldosterone antagonist
Sympathetic nervous system | Beta-blockers
Natriuretic and other vasodilator peptides | Neprilysin inhibitor (ARNI)
Sodium-glucose cotransporter-2  | SGLT2 inhibitors
Balanced vasodilation and oxidative stress modulation | Hydralazine/Isosorbide dinitrate
Elevated heart rate | Betablocker, Ivabradine
Guanylyl cyclase | Soluble guanylyl cyclase stimulator
Relief of congestion | Diuretic
Ventricul;ar arrhythmia | Implantable cardioverter defibrilator
Ventricular dyssynchrony due to conduction abnormalities | Cardiac resynchronization therapy
Mitral regurgitation | Surgical or percutaneous Mitral repair
Reduced aerobic capacity | Aerobic exercise training
The above table is adopted from 2021 AHA/ACC Guideline[2]

### Initiation, Titration, and Monitoring of Guideline-Directed Medical Therapy in HFrEF

[edit | edit source]

#### ACEi / ARB

[edit | edit source]

| ACEI / ARB|

|
|
|
|
|
|

| Initiate if ARNI is not accessible|

| Initiate dose based on indication|

| Titrate every 2 weeks
to target/max tolerated dose
with monitoring of blood pressure,
renal function, and potassium|

#### ARNi

[edit | edit source]

| ARNI|

|
|
|
|
|
|

| Initiate ≥36 hours after
discontinuing ACEI|

| Initiate dose based on indication|

24/26 mg twice daily
if taking enalapril ≤10 mg/day
or valsartan ≤160 mg/day|

| 49/51 mg twice daily
if taking enalapril >10 mg/day
or valsartan >160 mg/day|

| Reassess in 2 weeks
for tolerance, blood pressure,
electrolytes, and renal function
then titrate to 97/103 mg twice daily|

#### Beta-blocker

[edit | edit source]

| Beta blocker|

|
|
|
|
|
|

| Initiate dose based on indication|

| Titrate every 2 weeks
to target/max tolerated dose
with monitoring of heart rate
and blood pressure|

#### Mineralocorticoid Receptor Antagonist

[edit | edit source]

| MRA|

|
|
|
|
|
|

| Initiate dose based on indication|

| Titrate every 2 weeks
to target/max tolerated dose
with monitoring of electrolytes,
renal function, and clinical status|

#### SGLT2 Inhibitor

[edit | edit source]

| SGLT2 inhibitor|

|
|
|
|
|
|

| Initiate dose based on indication|

| Initiate dapagliflozin
if eGFR ≥30 mL/min/1.73 m²
or empagliflozin
if eGFR ≥20 mL/min/1.73 m²|

#### Diuretic

[edit | edit source]

| Diuretic|

|
|
|
|
|
|

| Initiate loop diuretic dose
based on renal function
and prior diuretic use|

| Titrate dose until recovery
of congestion with monitoring
of blood pressure, renal function,
and electrolytes|

| If persistent congestion on
high-dose loop diuretic,
consider alternative loop diuretic
or add thiazide diuretic|

#### Hydralazine / Isosorbide Dinitrate

[edit | edit source]

| Hydralazine / isosorbide dinitrate|

|
|
|
|
|
|

| Titrate every 2 weeks
to target/max tolerated dose
with monitoring of blood pressure|

### Drug-Specific Considerations

[edit | edit source]

Sacubitril/Valsartan | Ivabradine | SGLT2 Inhibitors

|
|

Indications

* HFrEF (EF ≤40%)
* NYHA class II–IV HF
* Use with background GDMT
* Used in place of an ACEI or ARB when feasible

| Indications

* Heart failure with reduced EF (≤35%)
* On maximum tolerated dose of beta-blocker
* Sinus rhythm with resting heart rate ≥70 beats/min
* NYHA class II or III HF

| Indications

* HFrEF (EF ≤40%) with or without diabetes
* NYHA class II–IV HF
* Combined with other treatment of heart failure

Contraindications

* Within 36 hours of ACEI use
* History of angioedema with or without an ACEI or ARB
* Pregnancy
* Lactation (no data)
* Severe hepatic impairment (Child-Pugh C)
* Concomitant aliskiren use in patients with diabetes
* Known hypersensitivity to either ARBs or ARNIs

| Contraindications

* HFpEF
* Presence of angina with normal EF
* Hypersensitivity
* Severe hepatic impairment (Child-Pugh C)
* Acute decompensated HF
* Blood pressure <90/50 mm Hg
* Sick sinus syndrome without a pacemaker
* Sinoatrial node block
* 2nd or 3rd degree block without a pacemaker
* Resting heart rate <60 beats/min
* Persistent AF or atrial flutter
* Atrial pacemaker dependence

| Contraindications

* Not approved for use in patients with type I diabetes due to increased risk of diabetic ketoacidosis
* Known hypersensitivity to drug
* Lactation (no data)
* On dialysis

Cautions

* Renal impairment:

Mild-to-moderate (eGFR 30-59 mL/min/1.73 m2): no starting dose adjustment required
* Severe (eGFR <30 mL/min/1.73 m2):

Reduce starting dose to 24/26 mg twice daily
Double dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily as tolerated
* Hepatic impairment:

Mild (Child-Pugh A): no starting dose adjustment required
Moderate (Child-Pugh B):
Reduce starting dose to 24/26 mg twice daily
Double dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily as tolerated
* Renal artery stenosis
* Systolic blood pressure <100 mm Hg
* Volume depletion

| Cautions

* Sinus node disease
* Cardiac conduction defects
* Prolonged QT interval

| Cautions

* For HF care, dapagliflozin in eGFR <30 mL/min/1.73 m2
* For HF care, empagliflozin in eGFR <20 mL/min/1.73 m2
* Pregnancy
* Increased risk of mycotic genital infections
* May contribute to volume depletion, altering diuretic dose if applicable
* For prevention of ketoacidosis in patients with diabetes:

Temporary discontinuation before scheduled surgery
Assess patients presenting with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level
* For prevention of acute kidney injury and renal impairment:

Temporarily discontinue in settings of reduced oral intake or fluid losses
* Urosepsis and pyelonephritis:

Evaluate for signs and symptoms of urinary tract infections and treat appropriately
* Necrotizing fasciitis of the perineum (Fournier’s gangrene):

Rare but life-threatening; assess for pain, erythema, swelling, fever, or malaise

The above table adopted from 2021 AHA/ACC Guideline[2]

| Ivabradine|

|
|
|
|
|
|

| Given Betablocker by maximum tolerable dose, sinus rhythm on ECG|

| Starting dose|

Age ≥ 75 years, 2.5 mg twice daily with food|

| Age <75 years, 5 mg twice daily with food|

| Evaluation of heart rate in 2-4 weeks|

Heart rate < 50 beats /min or symptoms of bradycardia|

| Heart rate 50-60 beats/ min|

| Heart rate>60 beats /min|

Reduced dose 2.5 mg twice daily with food, or discontinued if already on 2.5 mg twice daily|

| Maintaing current dose with monitoring heart rate|

| Increased dose by 2.5 mg twice daily until maximum dose of 7.5 mg twice daily, monitoring heart rate|

## References

[edit | edit source]

1. ↑ 1.0 1.1 Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (May 2022). "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". Circulation. 145 (18): e895–e1032. doi:10.1161/CIR.0000000000001063. PMID 35363499 Check `|pmid=` value (help).
2. ↑ 2.0 2.1 2.2 2.3 Maddox TM, Januzzi JL, Allen LA, Breathett K, Butler J, Davis LL, Fonarow GC, Ibrahim NE, Lindenfeld J, Masoudi FA, Motiwala SR, Oliveros E, Patterson JH, Walsh MN, Wasserman A, Yancy CW, Youmans QR (February 2021). "2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee". J Am Coll Cardiol. 77 (6): 772–810. doi:10.1016/j.jacc.2020.11.022. PMID 33446410 Check `|pmid=` value (help).

Template:WikiDoc Sources