Heart failure resident survival guide

For acute heart failure prevention click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahmoud Sakr, M.D. [2]; Ayokunle Olubaniyi, M.B,B.S [3]; Rim Halaby, M.D. [4] Nehal Eid, M.D.[5]

Acute Heart Failure Resident Survival Guide Microchapters
Overview
Classification
Causes
FIRE
Diagnosis
Treatment Stage A and B Stage C and D Diuretic Therapy Medication Dosages
Do's
Don'ts

Overview

Heart failure is a complex clinical syndrome characterized by impaired ventricular filling, impaired blood ejection, or both, leading to the inability of the heart to meet the metabolic demands of the body or to do so only at elevated filling pressures. The diagnosis relies on symptoms, physical examination findings, objective evidence of cardiac dysfunction, and supportive testing. The main symptoms and signs of heart failure include dyspnea, volume overload leading to pulmonary edema and/or peripheral edema, fatigue, and exercise intolerance. Acute decompensated heart failure (ADHF) is a life-threatening syndrome that can occur with new-onset heart failure or worsening of chronic heart failure. Symptoms and signs of ADHF may include dyspnea secondary to pulmonary edema, peripheral edema, hypotension, and impaired end-organ perfusion manifested by worsening renal function, altered mental status, oliguria, and cold clammy extremities.

The management of ADHF requires rapid identification of the precipitating cause, assessment of congestion and perfusion, oxygen or noninvasive ventilation when hypoxemia or respiratory distress is present, IV loop diuretic therapy for congestion, selective vasodilator therapy when blood pressure permits, and escalation to inotropes, vasopressors, invasive hemodynamic monitoring, or shock pathways when hypoperfusion is present. The goals of chronic heart failure treatment are to relieve symptoms, reduce hospitalization, improve survival, and prevent disease progression. Treatment of heart failure includes identification and management of precipitating factors, lifestyle modification, pharmacological therapy, device therapy when indicated, and referral for advanced therapies in selected patients.

Classification

Classification by Severity of Congestive Heart Failure

Shown below is a table comparing American College of Cardiology Foundation/American Heart Association (ACCF/AHA) stages to New York Heart Association (NYHA) functional classification of heart failure severity.

ACCF/AHA Stages		New York Heart Association (NYHA) Classification
Stage	Interpretation	Class	Interpretation
A	At high risk for heart failure but without structural heart disease or symptoms/signs of HF	-	-
B	Pre-HF: structural heart disease, increased filling pressures, or risk markers, but without symptoms/signs of HF	I	No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF
C	Structural heart disease with prior or current symptoms of HF	I	No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF
		II	Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF
		III	Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF
		IV	Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest
D	Advanced HF with marked symptoms that interfere with daily life and recurrent hospitalizations despite attempts to optimize GDMT	IV	Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest

Classification by Other Factors

Left Ventricular Ejection Fraction (LVEF)

• Heart failure with reduced ejection fraction (HFrEF): left ventricular ejection fraction (LVEF) ≤40%
• Heart failure with mildly reduced ejection fraction (HFmrEF): LVEF 41–49%
• Heart failure with preserved ejection fraction (HFpEF): LVEF ≥50%
• Heart failure with improved ejection fraction (HFimpEF): previous LVEF ≤40% with follow-up LVEF >40%

Cardiac Output

• Low-output heart failure
• High-output heart failure or high cardiac output state

Left vs. Right Sided

• Left-sided heart failure: pulmonary edema, pulmonary congestion, and dyspnea
• Right-sided heart failure: peripheral edema, elevated jugular venous pressure, hepatomegaly, ascites, and systemic venous congestion

Backward vs. Forward Failure

• Backward failure: congestion and elevated filling pressures
• Forward failure: low systemic perfusion and end-organ hypoperfusion

Causes

Life-Threatening Causes

Acute decompensated heart failure is life-threatening and should be treated promptly irrespective of the underlying cause.

Common Causes

• Acute coronary syndrome
• Acute kidney injury
• Acute severe myocarditis
• Cardiac arrhythmias
• Cardiomyopathy
• Cardiotoxic agents, including alcohol, cocaine, and anthracyclines
• Decompensation of underlying chronic heart failure
• Hypertensive crisis
• Pulmonary embolus
• Systemic inflammatory response syndrome or systemic infection
• Valvular heart disease
• Medication nonadherence
• Excess sodium or fluid intake
• Medications that worsen HF, including NSAIDs, nondihydropyridine calcium channel blockers, and thiazolidinediones

Click here for the complete list of causes.

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients with severe acute decompensated heart failure in need of immediate intervention.

Boxes in red signify that urgent management is needed.

Abbreviations: BUN: Blood urea nitrogen; COPD: Chronic obstructive pulmonary disease; D5W: 5% dextrose solution in water; HF: Heart failure; IV: Intravenous; MAP: Mean arterial pressure; Na: Sodium; NSAID: Non steroidal anti-inflammatory drug; SBP: Systolic blood pressure; S3: Third heart sound;

Identify cardinal findings that increase the pretest probability of acute decompensated heart failure ❑ Dyspnea ❑ Cool extremities ❑ Peripheral edema ❑ Decreased urine output ❑ Past medical history of heart failure ❑ History of orthopnea and paroxysmal nocturnal dyspnea ❑ Pulmonary crepitations/rales/crackles ❑ Third heart sound (S3)

Does the patient have any of the following findings that require hospitalization and urgent management? ❑ Severe decompensated HF: ❑ Hypotension (SBP <90 mm Hg or drop in MAP >30 mm Hg) and/or cardiogenic shock ❑ Altered mental status ❑ Cold and clammy extremities ❑ Urine output <0.5 mL/kg/hr ❑ Dyspnea at rest manifested by tachypnea or oxygen saturation <90% ❑ Atrial fibrillation with rapid ventricular response resulting in hypotension ❑ Suspected acute coronary syndrome

Yes

No

Admit to a level of care that allows continuous ECG monitoring, frequent vital signs, oxygen monitoring, and rapid escalation if needed

Proceed to complete diagnostic approach

Initial stabilization: ❑ Assess the airway ❑ Position the patient upright at an angle of approximately 45 degrees, with legs dependent if tolerated (decrease preload) ❑ Monitor heart rate and blood pressure continuously ❑ Monitor oxygen saturation continuously ❑ If hypoxemia is present (SaO2 <90% or PaO2 <60 mm Hg), administer oxygen with/without noninvasive ventilation ❑ Avoid routine morphine in ADHF; consider only in selected patients with severe pain or refractory distress after careful risk-benefit assessment ❑ Secure intravenous access with an appropriate IV cannula ❑ Monitor fluid intake and urine output carefully to guide diuretic adjustment Assess congestion and perfusion: Congestion at rest (dry vs. wet) "Wet" suggested by orthopnea, ↑JVP, rales/crackles, S3, pedal edema, ascites, or hepatomegaly Low perfusion at rest (warm vs. cold) "Cold" suggested by narrow pulse pressure, cool extremities, hypotension, altered mentation, or oliguria The patient is: ❑ Warm and dry, OR ❑ Warm and wet, OR ❑ Cold and dry, OR ❑ Cold and wet Identify precipitating factor and treat accordingly: Click on the precipitating factor for more details on the management ❑ Myocardial infarction ❑ Myocarditis ❑ Renal failure ❑ Hypertensive crisis ❑ Nonadherence to medications ❑ Worsening aortic stenosis or other severe valve disease ❑ Drugs (NSAIDs, nondihydropyridine calcium channel blockers, thiazolidinediones, or inappropriate beta-blocker use in unstable ADHF) ❑ Toxins (alcohol, anthracyclines, cocaine) ❑ Atrial fibrillation Rate control of atrial fibrillation may be required, but therapy must be selected according to hemodynamic stability and left ventricular systolic function. Avoid drugs with negative inotropic effects, such as nondihydropyridine calcium channel blockers including verapamil and diltiazem, in decompensated systolic heart failure. Consider cardioversion if the patient is in cardiogenic shock or if new-onset atrial fibrillation is the clear precipitant of hemodynamic decompensation. ❑ COPD ❑ Pulmonary embolism ❑ Anemia ❑ Thyroid abnormalities ❑ Systemic infection Treat congestion and optimize volume status: Diuretics ❑ Administer IV loop diuretics as intermittent boluses or continuous infusion when congestion is present ❑ If patient is already on loop diuretics: use an initial IV dose approximately 1 to 2.5 times the total daily home oral loop diuretic dose, adjusted for renal function, prior diuretic exposure, and severity of congestion ❑ If patient is not already on loop diuretics, administer an IV starting dose such as: Furosemide 40 to 80 mg IV, OR Bumetanide 0.5 to 1 mg IV Torsemide is generally used orally; IV torsemide is not available in the United States ❑ Adjust dose according to volume status, urine output, renal function, electrolytes, and congestion severity ❑ Perform serial assessment of fluid intake and output, vital signs, daily body weight (measured every day, with the same scale, at the same time, after first void), and symptoms ❑ Order daily electrolytes, BUN, creatinine, and magnesium during active IV diuresis ❑ Low sodium diet, commonly <2 g daily, unless contraindicated or individualized differently ❑ In case of inadequate response: ❑ Reassess within hours, double the IV loop diuretic dose when appropriate, and continue escalation based on urine output, weight change, renal function, electrolytes, and congestion status ❑ Add a second diuretic, such as a thiazide-type diuretic, only when response to moderate- or high-dose loop diuretic therapy is inadequate, with close electrolyte monitoring ❑ Do not use low-dose dopamine routinely to improve diuresis or renal blood flow; reserve vasoactive therapy for patients with hypotension, hypoperfusion, or shock ❑ Consider renal replacement therapy/ultrafiltration in selected patients with obvious volume overload refractory to optimized pharmacologic diuretic therapy Vasodilators ❑ Consider IV nitroglycerin or nitroprusside as add-on therapy to relieve dyspnea and reduce filling pressures in selected patients with hypertension or severe congestion without hypotension or organ hypoperfusion Do not administer vasodilators in patients with hypotension or worsening organ perfusion. Treat low perfusion: ❑ Inotropes or vasopressors may be required in patients with hypotension, hypoperfusion, low cardiac output, or cardiogenic shock If the patient is total body and intravascular volume overloaded and normotensive, then diuresis alone is usually appropriate. If the patient is volume overloaded but hypotensive or hypoperfused, then inotropes or vasopressors may be required in addition to diuretics. Invasive hemodynamic monitoring: ❑ Consider pulmonary artery catheterization in case of failure to respond to medical therapy, respiratory distress, shock, uncertainty regarding volume status, or worsening creatinine when the result will guide management; assess the following parameters: ❑ PCWP or PAWP ❑ Cardiac output ❑ Systemic vascular resistance VTE prevention: ❑ Pharmacologic VTE prophylaxis in the absence of contraindications Chronic medical therapy and GDMT during hospitalization: ❑ Chronic ACE inhibitor, ARB, or ARNI: hold or reduce if patient has hemodynamic instability, symptomatic hypotension, severe AKI, or clinically significant hyperkalemia ❑ Chronic beta blocker: Hold or reduce if patient is in shock, severely hypotensive, bradycardic, or requiring escalating inotropes or vasopressors Continue when possible if patient is hemodynamically stable and not hypoperfused ❑ Do not initiate or uptitrate ACE inhibitors, ARBs, or ARNI during hemodynamic instability, shock, symptomatic hypotension, severe AKI, or clinically significant hyperkalemia ❑ Initiate or resume RAAS inhibition before discharge once clinically stable, renal function is acceptable, and potassium is acceptable ❑ Do not initiate beta blockers during the unstable or hypoperfused phase of ADHF ❑ Initiate or resume evidence-based beta blockers before discharge once the patient is euvolemic, off IV inotropes/vasopressors, and clinically stable ❑ Initiate SGLT2 inhibitor therapy during hospitalization once clinically stable and eGFR is acceptable, unless contraindicated Monitor laboratory tests: ❑ BUN ❑ Creatinine ❑ Sodium, chloride, bicarbonate, potassium, and magnesium during active diuresis and medication titration Management of hyponatremia: ❑ Water restriction when clinically appropriate ❑ Consider <2 L/day if Na is <130 mEq/L ❑ Consider <1 L/day if Na is <125 mEq/L, individualized to clinical status Keep in mind that juices are essentially free water with sugar. In the hyponatremic patient, avoid unnecessary D5W-containing infusions. ❑ Optimize HF therapy and decongestion ❑ Consider short-term vasopressin antagonist therapy only in selected patients with persistent clinically significant hypervolemic hyponatremia despite standard management

Complete Diagnostic Approach

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

Abbreviations: ANA: Antinuclear antibody; ARDS: Acute respiratory distress syndrome; BNP: B-type natriuretic peptide; BUN: Blood urea nitrogen; CAD: Coronary artery disease; CBC: Complete blood count; CCB: Calcium channel blocker; CHF: Congestive heart failure; CT: Computed tomography; CXR: Chest X-ray; DM: Diabetes mellitus; ECG: Electrocardiogram; JVP: Jugular venous pressure; HF: Heart failure; HTN: Hypertension; LVEF: Left ventricular ejection fraction; LVH: Left ventricular hypertrophy; MI: Myocardial infarction; MRI: Magnetic resonance imaging; NT-proBNP: N-terminal pro-brain natriuretic peptide; OCPs: Oral contraceptive pills; PAWP: Pulmonary artery wedge pressure; SBP: Systolic blood pressure; S1: First heart sound; S3: Third heart sound; TSH: Thyroid stimulating hormone

Characterize the symptoms: Symptoms of left-sided fluid accumulation: ❑ Dyspnea ❑ At rest ❑ Exertional ❑ Paroxysmal nocturnal dyspnea ❑ Orthopnea ❑ Cough Symptoms of right-sided fluid accumulation: ❑ Peripheral edema ❑ Right upper quadrant abdominal discomfort ❑ Bloating ❑ Early Satiety Symptoms of reduced cardiac output: ❑ Fatigue ❑ Exercise intolerance ❑ Oliguria ❑ Dizziness ❑ Syncope ❑ Altered mental status ❑ Cyanosis ❑ Anorexia ❑ Abdominal pain (suggestive of mesenteric ischemia) Symptoms suggestive of precipitating events: ❑ Chest pain (suggestive of myocardial ischemia) ❑ Palpitations (suggestive of arrhythmias) ❑ Fever (suggestive of infection) Nonspecific symptoms: ❑ Nausea ❑ Unintentional Weight loss Obtain a detailed history: ❑ Past medical history ❑ Atrial fibrillation ❑ Cardiomyopathy ❑ Diabetes mellitus ❑ Hypertension ❑ Myocarditis ❑ Previous myocardial infarction ❑ Prior heart failure ❑ Sleep apnea ❑ Thyroid disease ❑ Valvular heart disease ❑ Medication history ❑ Nonadherence with previously prescribed medications for heart failure ❑ Intake of drugs that may worsen HF or cause cardiomyopathy: ❑ Alcohol ❑ Beta blockers if newly started or excessive in unstable decompensation ❑ Calcium channel blockers, especially nondihydropyridine agents such as verapamil and diltiazem, which may worsen HFrEF ❑ Chemotherapy drugs, especially anthracyclines ❑ NSAIDs ❑ Thiazolidinediones ❑ Family history ❑ History of dilated cardiomyopathy ❑ Sudden cardiac death ❑ Prior Radiation to the chest Determine the NYHA classification based on symptoms: ❑ Class I (no symptoms) ❑ Class II (symptoms with ordinary activities) ❑ Class III (symptoms with less than ordinary activity) ❑ Class IV (symptoms at rest)

Examine the patient: General appearance: ❑ Ill-looking ❑ In respiratory distress ❑ In upright sitting position Vitals: ❑ Temperature ❑ Fever (suggestive of underlying infection) ❑ Pulse ❑ Tachycardia ❑ Narrow pulse pressure (<25% of SBP) ❑ Blood pressure ❑ Hypotension (suggestive of circulatory collapse or shock) ❑ Hypertension ❑ Respiration ❑ Tachypnea ❑ Pulse oximetry; administer oxygen if hypoxemic, generally targeting SpO2 ≥90–92%, with individualized lower targets in patients at risk of hypercapnic respiratory failure Weight: ❑ Measure weight daily at the same time after the first void ❑ Compare current weight with known dry weight to estimate the extent of volume overload Skin ❑ Cool and clammy (suggestive of hypoperfusion) ❑ Cyanosis (suggestive of severe hypoxemia) ❑ Anasarca ❑ Jaundice (suggestive of liver dysfunction secondary to right-sided congestion or hypoperfusion) Neck examination: ❑ Jugular vein distention (suggestive of elevated right-sided filling pressure) ❑ Positive hepatojugular reflux (suggestive of elevated right-sided filling pressure) Respiratory examination ❑ Tachypnea ❑ Wheeze ❑ Dullness at lung bases (suggestive of pleural effusion) ❑ Crackles/crepitations/rales (suggestive of pulmonary congestion or edema) ❑ Cheyne-stokes respiration Cardiovascular examination ❑ Displaced apex beat (suggestive of enlarged left ventricle) ❑ Parasternal heave (suggestive of elevated right ventricular pressure) ❑ S3 or S4 or both ❑ Soft S1 ❑ Pulsus alternans ❑ New or changed murmur (suggestive of underlying valvular heart disease) ❑ Mitral regurgitation - Holosystolic murmur ❑ Aortic regurgitation - Decrescendo diastolic murmur ❑ Aortic stenosis - Crescendo-decrescendo systolic ejection murmur with or without ejection click Abdominal examination The following findings suggest volume overload and/or poor forward cardiac output: ❑ Hepatojugular reflux ❑ Hepatomegaly ❑ Ascites Extremity examination ❑ Pedal edema Neurological examination ❑ Altered mental status ❑ Syncope (suggestive of aortic stenosis, malignant arrhythmia, severe hypotension, or pulmonary embolism) Determine status of congestion and perfusion based on physical exam: Congestion at rest (dry vs. wet) "Wet" suggested by orthopnea, ↑JVP, positive hepatojugular reflux, abnormal valsalva response, rales/crackles, dullness upon percussion at bases, S3, peripheral edema, hepatomegaly, ascites, or jaundice Low perfusion at rest (warm vs. cold) "Cold" suggested by narrow pulse pressure, cool extremities, hypotension, soft S1, pulsus alternans, decreased urinary output, altered mentation, or worsening renal function The patient is: ❑ Warm and dry, OR ❑ Warm and wet, OR ❑ Cold and dry, OR ❑ Cold and wet

Order tests: Routine initial tests ❑ CBC (rule out anemia and infection) ❑ Troponin ❑ May be elevated in myocardial ischemia, myocardial injury, and acute cardiogenic pulmonary edema, particularly if creatinine clearance (CrCl) is reduced ❑ Troponin T ≥0.1 ng/mL has been associated with poor prognosis in acute cardiogenic pulmonary edema ❑ Electrolytes ❑ Sodium: hyponatremia may occur due to water retention and neurohormonal activation ❑ Serum calcium ❑ Serum magnesium can be lowered by diuresis ❑ Serum bicarbonate: to monitor contraction alkalosis with diuresis ❑ BUN, creatinine: may be elevated due to poor renal perfusion, venous congestion, intrinsic renal disease, or medications ❑ Urinalysis when renal disease, infection, or proteinuria is suspected ❑ Glucose ❑ Fasting lipid profile for cardiovascular risk assessment when clinically appropriate ❑ Liver function tests: can be elevated secondary to congestion or hypoperfusion ❑ TSH ❑ BNP or NT-proBNP, especially if the diagnosis is uncertain Acute heart failure is unlikely if: ❑ BNP ≤100 pg/mL, or ❑ NT-proBNP ≤300 pg/mL These are acute HF rule-out thresholds; lower rule-out thresholds are used for chronic or ambulatory HF. ❑ Chest X-ray ❑ Cardiomegaly (cardiothoracic ratio >50%) ❑ Cardiogenic pulmonary edema ❑ Kerley B lines ❑ Peribronchial cuffing ❑ Cephalization Chest X-ray findings in a patient with acute heart failure ❑ ECG to help identify the cause of heart failure ❑ Low QRS voltage (suggestive of infiltrative cardiomyopathy, pericardial effusion, obesity, or COPD) ❑ Arrhythmia, including atrial fibrillation ❑ Poor R wave progression (suggestive of prior MI) ❑ Left ventricular hypertrophy (consistent with history of hypertension) ❑ Left bundle branch block (LBBB) due to prior MI or cardiomyopathy, may contribute to dyssynchrony ❑ Left atrial enlargement due to valvular disease, hypertension, or chronically elevated filling pressures ❑ Non-specific ST segment and T wave changes may suggest ischemia ❑ 2-D echocardiography with Doppler ❑ Assess chamber size, wall thickness, wall motion, valve function, pulmonary pressures, and pericardial disease ❑ Assess ejection fraction ❑ Radionuclide ventriculography or MRI when echocardiography is inadequate or when myocardial scar, infiltrative disease, inflammation, or cardiomyopathy etiology requires further evaluation ❑ Coronary angiography or coronary CT angiography when CAD or ACS is suspected and results would change management ❑ Consider pulmonary artery catheterization in case of failure to respond to medical therapy, respiratory distress, shock, uncertainty regarding volume status, or worsening creatinine when invasive measurements will guide therapy; assess the following parameters: ❑ PCWP/PAWP ❑ Cardiac output ❑ Systemic vascular resistance Order additional tests selectively to evaluate alternative or specific etiologies: ❑ ANA and rheumatoid factor when rheumatologic disease is suspected ❑ Diagnostic tests for hemochromatosis, amyloidosis, sarcoidosis, or other infiltrative diseases when clinically suspected ❑ Diagnostic tests for pheochromocytoma when clinical features suggest catecholamine excess ❑ Endomyocardial biopsy only in selected patients when myocarditis, infiltrative disease, or unexplained cardiomyopathy is suspected and biopsy results would affect treatment

Consider alternative diagnoses: Alternative diagnoses Features Acute asthma ❑ Wheeze ❑ Reversal of symptoms following administration of bronchodilators COPD ❑ Increased cough ❑ Increased dyspnea ❑ Increased sputum production ARDS ❑ Severe hypoxia ❑ Bilateral opacities on chest X-ray ❑ PCWP usually not elevated from left-sided filling pressure alone Pneumonia ❑ Fever, cough, sputum ❑ Consolidation on chest X-ray Pulmonary embolism ❑ Pleuritic chest pain, cough, acute dyspnea, hypoxemia, or syncope ❑ Risk factors: trauma, immobilization, smoking, OCPs, active cancer, thrombophilia ❑ Clot in pulmonary artery on CT pulmonary angiography

Assess the stage of heart failure using the ACCF/AHA staging system to guide chronic therapy

Stage C ❑ Patients with structural heart disease This refers to patients with the following: ❑ Previous MI ❑ LV remodeling* (including LVH and low EF) ❑ Symptomatic valvular disease or other structural heart disease AND ❑ Prior or current signs or symptoms of heart failure *LV remodeling refers to changes in size, shape, and function of the heart resulting from cardiac load or injury

Stage D ❑ Advanced/refractory heart failure ❑ Marked symptoms at rest ❑ Recurrent hospitalizations ❑ Progressive intolerance to GDMT ❑ Need for advanced therapies, palliative care, or transplant/LVAD evaluation

Prevention of Heart Failure in Stage A and B

Shown below is an algorithm depicting the management of stage A and B heart failure.

Abbreviations: ACE I: Angiotensin converting enzyme inhibitor; ACS: Acute coronary syndrome; CVD: Cardiovascular disease; DM: Diabetes mellitus; EF: Ejection fraction; HF: Heart failure; HTN: Hypertension; ICD: Implantable cardioverter defibrillator; MI: Myocardial infarction; PAD: Peripheral artery disease; SGLT2: Sodium-glucose cotransporter 2

What is the stage of heart failure (HF)?

Stage A At high risk for HF but without structural heart disease or symptoms/signs of HF

Stage B / Pre-HF Structural heart disease, increased filling pressures, or risk markers but without symptoms/signs of HF

❑ Encourage healthy lifestyle and regular physical activity ❑ Treat hypertension ❑ Treat dyslipidemia according to ASCVD risk ❑ Control obesity and promote weight reduction when appropriate ❑ Treat DM and optimize cardiometabolic risk ❑ In patients with type 2 diabetes and established cardiovascular disease or high cardiovascular risk, consider SGLT2 inhibitors to reduce the risk of HF hospitalization ❑ Avoid tobacco ❑ Avoid cardiotoxic agents when possible ❑ Administer ACE-I or ARB when indicated for HTN, DM, CVD, PAD, CKD, or other guideline-supported indications

❑ Encourage healthy lifestyle and regular physical activity ❑ Treat hypertension ❑ Treat dyslipidemia according to ASCVD risk ❑ Control obesity and treat DM ❑ Avoid tobacco and cardiotoxic agents ❑ Continue GDMT in patients with HFimpEF to prevent relapse of HF and LV dysfunction

Consider additional measures in selected patients: ❑ Administer ACE-I or ARB if history of MI or ACS and reduced EF to prevent HF symptoms and reduce mortality; use in all patients with reduced EF when indicated and tolerated ❑ Administer evidence-based beta-blockers if history of MI or ACS and reduced EF, and in all reduced EF when indicated and tolerated ❑ Administer statins if history of MI, ACS, or other ASCVD indication ❑ Consider ICD placement to prevent sudden death if ischemic cardiomyopathy, >40 days post-MI, ≥90 days post-revascularization when applicable, after adequate GDMT optimization, LVEF ≤30%, NYHA class I, and expected meaningful survival >1 year

Treatment of Heart Failure in Stage C and D

Shown below is an algorithm depicting the management of stage C and D heart failure.

Abbreviations: ACE I: Angiotensin converting enzyme inhibitor; ARB: Angiotensin II receptor blocker; ACS: Acute coronary syndrome; ARNI: Angiotensin receptor-neprilysin inhibitor; BID: Twice a day; BNP: Brain natriuretic peptide; CRT: Cardiac resynchronization therapy; CVD: Cardiovascular disease; DM: Diabetes mellitus; EF: Ejection fraction; GDMT: Guideline-directed medical therapy; GFR: Glomerular filtration rate; HF: Heart failure; HFimpEF: Heart failure with improved ejection fraction; HFmrEF: Heart failure with mildly reduced ejection fraction; HFrEF: Heart failure with reduced ejection fraction; HFpEF: Heart failure with preserved ejection fraction; HTN: Hypertension; ICD: Implantable cardioverter defibrillator; LVEF: Left ventricular ejection fraction; MCS: Mechanical circulatory support; MRA: Mineralocorticoid receptor antagonist; NYHA: New York Heart Association; MI: Myocardial infarction; PAD: Peripheral artery disease; SGLT2: Sodium-glucose cotransporter 2; TID: Three times a day

HFrEF Stage C Medical Treatment

Foundational GDMT Framework

For patients with symptomatic chronic HFrEF, contemporary guideline-directed medical therapy is built around four foundational medication classes. When feasible, the usual strategy is to add all foundational classes before focusing on maximal uptitration of any single class, with individualized sequencing according to blood pressure, renal function, potassium, heart rate, congestion, and tolerability.

1. ARNI preferred, or ACE inhibitor/ARB when ARNI is not feasible
2. Evidence-based beta blocker
3. Mineralocorticoid receptor antagonist (MRA)
4. SGLT2 inhibitor

Additional therapies such as hydralazine/isosorbide dinitrate, ivabradine, vericiguat, digoxin, ICD, CRT, cardiac rehabilitation, palliative care, mechanical circulatory support, or transplant evaluation are used in selected patients.

Medications

Drug Class	Drug	Daily dose	Maximum daily dose / Notes
Loop diuretics	Furosemide (duration of action: 6 to 8 h)	PO dose for chronic HF: 20 to 40 mg once or twice daily IV dose for acute HF: Initial dose given slowly over 1 to 2 minutes ❑ If patient is already on loop diuretics: initial IV total daily dose approximately 1 to 2.5 times the home oral daily dose ❑ If patient is not already on loop diuretics: common starting dose 40 to 80 mg IV ❑ Reassess urine output and symptoms within hours and escalate as needed Continuous IV infusion: Initial IV bolus administered slowly over 1 to 2 minutes, then continuous IV infusion rate individualized to response || Up to 600 mg/day may be used in severe edematous states with close monitoring; many hospitalized HF protocols escalate to high-dose furosemide equivalents based on response
	Bumetanide (duration of action: 4 to 6 h)	PO dose for chronic HF: 0.5 to 1.0 mg once or twice daily IV dose may be used for acute HF; approximate equivalence: bumetanide 1 mg ≈ furosemide 40 mg	10 mg/day
	Torsemide (duration of action: 12 to 16 h)	PO dose for chronic HF: 10 to 20 mg once daily	200 mg/day; torsemide is generally used orally and IV torsemide is not available in the United States
Thiazide diuretics	Chlorothiazide (duration of action: 6 to 12 h)	PO: 250 to 500 mg once or twice daily; IV chlorothiazide may be used in selected hospitalized patients with diuretic resistance	1000 mg/day
	Hydrochlorothiazide (duration of action: 6 to 12 h)	PO: 25 mg once or twice daily	200 mg/day
	Metolazone (duration of action: 12 to 24 h)	PO: 2.5 mg once daily when used for sequential nephron blockade	20 mg/day; monitor electrolytes closely
K+-sparing diuretic	Amiloride (duration of action: 24 h)	PO: 5 mg once daily	20 mg/day; avoid routine combination with MRA because of hyperkalemia risk
	Spironolactone (duration of action: 1 to 3 h)	PO: 12.5 to 25.0 mg once daily	50 mg/day; monitor potassium and renal function
	Triamterene (duration of action: 7 to 9 h)	PO: 50 to 75 mg twice daily	200 mg/day; avoid routine combination with MRA because of hyperkalemia risk
ACE inhibitors	Enalapril	2.5 mg twice daily	10 to 20 mg twice daily
	Lisinopril	2.5 to 5 mg once daily	20 to 40 mg once daily
	Ramipril	1.25 to 2.5 mg once daily	10 mg once daily
ARBs	Candesartan	4 to 8 mg once daily	32 mg once daily
	Losartan	25 to 50 mg once daily	50 to 150 mg once daily
	Valsartan	20 to 40 mg twice daily	160 mg twice daily
ARNI Foundational GDMT for HFrEF	Sacubitril/valsartan	24 mg sacubitril/26 mg valsartan twice daily in patients with SBP 100–120 mm Hg, low prior ACE inhibitor/ARB dose, or renal/hepatic impairment; otherwise 49 mg sacubitril/51 mg valsartan twice daily	97 mg sacubitril/103 mg valsartan twice daily; discontinue ACE inhibitor for at least 36 hours before starting ARNI
Beta blockers Foundational GDMT for HFrEF	Bisoprolol	1.25 mg once daily	10 mg once daily
	Carvedilol	3.125 mg twice daily	50 mg twice daily
	Carvedilol CR	10 mg once daily	80 mg once daily
	Metoprolol succinate extended release	12.5 to 25.0 mg once daily	200 mg once daily
Aldosterone antagonists / MRAs Foundational GDMT for HFrEF	Spironolactone	12.5 to 25.0 mg once daily	25 mg once or twice daily; monitor potassium and renal function
	Eplerenone	25 mg once daily	50 mg once daily
SGLT2 inhibitors Foundational GDMT for HFrEF; recommended in HFmrEF/HFpEF to reduce HF hospitalization and cardiovascular events	Dapagliflozin	10 mg once daily	No titration required
	Empagliflozin	10 mg once daily	No titration required
Inotropes	Dopamine	5 to 10 mcg/kg/min, OR 10 to 15 mcg/kg/min depending on hemodynamic goal	Reserve for selected patients with hypotension or shock; not recommended routinely for renal protection or enhanced diuresis
	Dobutamine	2.5 to 5 mcg/kg/min initially; titrate as needed, often 5 to 20 mcg/kg/min	Use for low-output states or cardiogenic shock when indicated
	Milrinone	0.125 to 0.75 mcg/kg/min	Adjust for renal function; loading dose often avoided in unstable or hypotensive patients
Vasodilators	Nitroglycerin	5 to 10 mcg/min initially; increase by 5 to 10 mcg/min every 3 to 5 minutes as tolerated	May be titrated to high doses in hypertensive pulmonary edema with close blood pressure monitoring
	Nitroprusside	0.3 mcg/kg/min initially; titrate carefully according to blood pressure and clinical response	Common range 0.3 to 5 mcg/kg/min; high-dose or prolonged use increases cyanide/thiocyanate toxicity risk; close monitoring required
	Nesiritide	2 mcg/kg bolus; then 0.01 mcg/kg/min continuous infusion	Max 0.03 mcg/kg/min; not routinely used because outcome benefit is not established
Digoxin	Digoxin	Loading dose: usually not required for chronic HF; if used for rate control, individualize by renal function, age, and urgency Maintenance dose: commonly 0.125 mg daily in older patients or renal impairment; 0.25 mg daily may be used in selected younger patients with normal renal function || Monitor renal function, electrolytes, and serum digoxin concentration. Drugs that increase digoxin concentration include amiodarone, quinidine, and verapamil
Add-On Therapies Beyond the Four Pillars 1. Hydralazine and isosorbide dinitrate	Fixed-dose combination	37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily	75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily
	Individual doses	Hydralazine: 25 to 100 mg 3 or 4 times daily Isosorbide dinitrate: 20 to 40 mg 3 times daily	Hydralazine: 300 mg daily in divided doses Isosorbide dinitrate: 120 mg daily in divided doses
2. Ivabradine	Ivabradine	5 mg twice daily with meals (2.5 mg twice daily if history of conduction disease or bradycardia risk)	7.5 mg twice daily; titrate to resting heart rate 50-60 bpm when indicated
3. Vericiguat	Vericiguat	2.5 mg once daily	10 mg once daily

Referral for Advanced Therapies

The "I-NEED-HELP" mnemonic identifies patients who may benefit from referral to an advanced HF center:

• Inotropes (previous or ongoing requirement)
• NYHA class III-IV or persistently elevated natriuretic peptides
• End-organ dysfunction (worsening renal/hepatic function)
• Ejection fraction ≤35%
• Defibrillator shocks (recurrent)
• Hospitalizations (>1 HF hospitalization in 12 months)
• Edema (refractory despite escalating diuretics)
• Low blood pressure (SBP consistently ≤90 mm Hg)
• Progressive intolerance to GDMT

Specific referral triggers include:

• • ≥2 HF hospitalizations or ED visits in 12 months
  • Progressive decline in renal function
  • Intolerance to RAAS inhibitors due to hypotension or renal dysfunction
  • Inability to walk 1-2 blocks due to dyspnea or fatigue
  • Worsening right HF or secondary pulmonary hypertension
  • Frequent SBP ≤90 mm Hg
  • Cardiac cachexia
  • Persistent hyponatremia (Na <134 mEq/L)
  • Refractory or recurrent ventricular arrhythmias; frequent ICD shocks
  • Predicted 1-year mortality >20% using validated risk models when available

The "Golden Window" for referral: Patients should be referred before progressive or irreversible end-organ damage has occurred.

Do's

Acute Decompensated Heart Failure

• Differentiate systolic and diastolic heart failure among patients with ADHF in order to guide therapy:
  • Inotropic agents are not used routinely in ADHF, but may be indicated in patients with systolic dysfunction and evidence of hypoperfusion, low cardiac output, or cardiogenic shock.
  • While beta blocker initiation is generally avoided during the unstable or hypoperfused phase of acute decompensated systolic heart failure, control of tachycardia may be useful in selected stable patients, especially those with diastolic heart failure, to prolong left ventricular filling time.
  • ACE inhibitors, ARBs, or ARNI may be continued, resumed, or initiated once the patient is hemodynamically stable and renal function and potassium are acceptable; avoid initiation or uptitration during shock, symptomatic hypotension, severe AKI, or clinically significant hyperkalemia.
• Rely on the patient's volume status, congestion, renal function, perfusion, and urine output to guide the aggressiveness of diuresis in ADHF.
• Continue chronic medications during acute decompensation in the following conditions:
  • ACE inhibitor/ARB/ARNI: may be continued if the patient is hemodynamically stable without severe AKI, symptomatic hypotension, or clinically significant hyperkalemia
  • Beta blocker: may be continued in the absence of hypotension, shock, severe bradycardia, or need for escalating inotropes/vasopressors
  • Aldosterone antagonist: may be continued in the absence of hypotension, hyperkalemia, and significant renal dysfunction
• Digoxin may reduce heart failure hospitalizations but has not shown a mortality benefit in HFrEF. It can be used in selected patients with HFrEF and atrial fibrillation to help reduce ventricular response, especially when beta blockers are not tolerated or insufficient. Lower serum digoxin concentrations are generally preferred, particularly in older patients and patients with renal impairment. Drugs that increase the concentration of digoxin include amiodarone, quinidine, and verapamil.
• DVT prophylaxis unless contraindicated.
• Consider adding another diuretic, such as metolazone or a thiazide-type diuretic, for worsening congestion despite adequate loop diuretic escalation, with close electrolyte and renal monitoring.
• Daily serum electrolytes, BUN, creatinine, and magnesium should be measured during IV diuresis or active titration of heart failure medications.
• Convert IV diuretics to oral therapy in anticipation of discharge once the patient is clinically stable and adequately decongested.
• Schedule early follow-up visit within 7 to 14 days and early telephone follow-up within 2 to 3 days of hospital discharge.

Chronic Heart Failure

• Guideline-directed medical therapy (GDMT) for HFrEF includes four foundational medication classes: ARNI/ACE inhibitor/ARB, evidence-based beta blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor. Additional therapies, such as hydralazine/isosorbide dinitrate, ivabradine, vericiguat, digoxin, ICD, CRT, cardiac rehabilitation, palliative care, or advanced HF therapies, are used in selected patients.
• Order an echocardiogram as soon as possible in the absence of a recent one or if the patient's clinical status is deteriorating.
• Continue GDMT in patients with HFimpEF unless contraindicated, because withdrawal may lead to relapse of LV dysfunction and HF.

Don'ts

• Avoid, if possible, NSAIDs, sympathomimetics, tricyclic antidepressants, class I antiarrhythmics, most class III antiarrhythmics except amiodarone when appropriate, and nondihydropyridine calcium channel blockers such as diltiazem and verapamil in patients with HFrEF or acute decompensated HF, as they can be harmful.
• Do not administer parenteral inotropes in normotensive patients with acute decompensated HF without evidence of decreased organ perfusion or shock.
• Do not use low-dose dopamine routinely to improve diuresis or renal blood flow.
• Do not combine an ACEI, ARB, and aldosterone antagonist in patients with HFrEF unless there is a compelling specialist-directed indication, because this combination increases risk of renal dysfunction and hyperkalemia.
• Do not use aldosterone receptor antagonists in patients with hyperkalemia or significant renal insufficiency when serum creatinine is more than 2.5 mg/dL in men or more than 2.0 mg/dL in women, estimated glomerular filtration rate <30 mL/min/1.73 m2, or potassium more than 5.0 mEq/L.
• Do not use statins routinely for heart failure alone without another indication such as ASCVD, diabetes, or primary prevention based on cardiovascular risk.
• Do not administer K⁺-sparing diuretics such as amiloride or triamterene together with an aldosterone antagonist unless specifically directed and closely monitored, because of elevated risk of hyperkalemia.
• Do not initiate or uptitrate RAAS inhibitors, ARNI, beta blockers, or MRA during shock, severe hypotension, severe AKI, or clinically significant hyperkalemia; wait until the patient is clinically stable and monitoring is in place.
• Do not delay advanced HF referral until irreversible end-organ dysfunction has developed.

References