Congestive heart failure pharmacotherapy

Congestive Heart Failure Microchapters

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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

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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

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

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Abbreviations: ACE-I: Angiotensin-converting enzyme inhibitor; ARNI: Angiotensin receptor-neprilysin inhibitor; CRT-D: cardiac resynchronization therapy with defibrillator ; CRT-P: cardiac resynchronization therapy with pacemaker; ICD: Implantable cardioverter-defibrillator; HFrEF: Heart failure with reduced ejection fractio;

| Management of HFrEF|

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| (Class I)

* ACE-I/ARNI
* Beta-blocker
* Mineralocorticoid receptor antagonist
* Dapagliflozin/Empagliflozin
* Loop diuretic for fluid retention

| LVEF ≤35% and QRS <130 ms|

| LVEF >35% or device

therapy not indicated

or inappropriate|

| Sinus rhythm and LVEF ≤35% and QRS ≥130 ms

| ICD implantation

* Ischemic (class I)
* Non-ischemic (class IIa)

| If symptoms persist, consider therapies (class II)|

| CRT-D/-P
* QRS ≥150 ms (Class I)
* QRS 130-149 ms (Class IIa)

The above table adopted from 2021 ESC Guideline

[1]

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

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[2]

Pathophysiology  | Treatment

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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 adopted from 2021 AHA/ACC Guideline

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

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| Heart failure  reduced EF, stage C, treatment|

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| 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|

The above algorithm adopted from 2021 AHA/ACC Guideline

| ACEI, ARB|

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| Starting in patient if ARNI is not accessible|

| Dosage initiation based on indication|

| Increasing dose every 2 weeks until achieving target dose or maximum tolerance and monitoring of blood pressure, renal function, potassium after initiation and during titration|

| ARNI|

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| Initiation after 36 hours of discontinuing ACEI, if the patient is on ACEI|

| Dosage initiation based on indication|

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

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

| In 2 weeks assessment about tolerance, blood pressure, electrolytes, renal function and dosage titration to target of 97/103 mg twice daily|

| Diuretics|

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| Initiation loop diuretic dose based on renal function, previous use of diuretics|

| Titration dose until recovery of congestion, reducing dose in concomitant administration of ACEI, ARB, ARNI, monitoring blood pressure, renal function, electrolytes after initiation and during titration dose|

| In high dose of loop diuterics (80 mg furosemide twice daily), Considering other type of loop diuretics or adding thiazide to loop diuretic by monitoring of blood pressure, renal function, electrolytes after initiation dose or during titration|

| SGLT2 inhibitor|

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| Dosage initiation based on indication|

| Initiation dapaglifelozin in eGFR≥ 30 mL/min/1.73 m², and empagliflozin in eGFR≥ 20 mL/ min/1.73 m²|

| Betablocker|

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| Dosage initiation based on indication|

| Dosage titration every two weeks until achieving target dose or maximum tolerance, monitoring heart rate , blood pressure after initiation and during titration|

| Aldosterone antagonist|

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| Dosage initiation based on indication|

| Increase dose every 2 weeks up to maximum dose or achieving tolerated dose, monitoring electrolytes and renal function at 2-3 days following initiation then 7 days after initiation or titration, then monthly for 3 months and every 3 months afterward, clinical status monitoring|

| Hydralazine, isosorbide dinitrate|

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| Increase dose every 2 weeks until target dose or achieving tolerated dose with monitoring of blood pressure|

* Indications for use of an ARNI

Heart failure reduced EF (HFrEF) (LVEF ≤ 40%)
NYHA 2-4 heart failure
Use in place of ACEI or ARB for combination therapy of heart failure

* Indications for Use of Ivabradine

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

* Indications for Use of an SGLT2 Inhibitor

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

* Dose adjustment of sacubitril-valsartan

49/51 twice daily:

Previous use of high dose of ACEI or ARB: valsartan 160 mg daily or enalapril 10 mg daily
24/46 mg twice daily:

valsartan<160 mg daily, enalapril < 10 mg daily
No previous use of ACEI or ARB
Severe renal impairment (eGFR <30 mL/min/1.73 m2)
Moderate hepatic impairment (Child-Pugh Class B)
Elderly (age ≥75 years)

Sacubitril/Valsartan |  Ivabradine | SGLT2 Inhibitors

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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

Causions

* 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 the 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 the 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

| Causions

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

| Causions

* 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 who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level

For prevention of acute kidney injury and renal impairment: temporarily discontinuing in settings of reduced oral intake or fluid losses
* Urosepsis and pyelonephritis: evaluation for signs and symptoms of urinary tract infections and treatment
* Necrotizing fasciitis of the perineum (Fournier’s gangrene): rare, serious, life-threatening cases, assessment of pain or tenderness,

erythema, or swelling in the genital  or perineal area, along with fever or malaise

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

| Ivabradine|

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| 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|

* Starting dose of Ivabradine

If the patient taking maximum tolerated dose of betablocker but resting heart rate ≥ 70 beat/min , Ivabradine 5 mg twice a day with food is recommended.
In the presence of conduction abnormality, age≥ 75 years, Ivabradine 2.5 mg twice a day with food is considered.

## References

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1. ↑ McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland J, Coats A, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam C, Lyon AR, McMurray J, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano G, Ruschitzka F, Kathrine Skibelund A (September 2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check `|pmid=` value (help). Vancouver style error: initials (help)
2. ↑ 2.0 2.1 Bozkurt B, Hershberger RE, Butler J, Grady KL, Heidenreich PA, Isler ML, Kirklin JK, Weintraub WS (April 2021). "2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure)". Circ Cardiovasc Qual Outcomes. 14 (4): e000102. doi:10.1161/HCQ.0000000000000102. PMC 8059763 Check `|pmc=` value (help). PMID 33755495 Check `|pmid=` value (help).

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