Congestive heart failure pharmacotherapy

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Acute Pharmacotherapy
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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
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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
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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
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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]

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

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

(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

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

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 adopted from 2021 AHA/ACC Guideline

Treatment Algorithm for Guideline-Directed Medical Therapy Including Novel Therapies

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

The above algorithm adopted from 2021 AHA/ACC Guideline

ACEI, ARB

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

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

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

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

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

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

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
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

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

• 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.