SUMMARY: 

Heart failure (HF) is a broad term that encompasses many different etiologies and degrees of cardiac dysfunction, but generally refers to the inability of the heart to pump effectively. Americans over 40 have a 20% lifetime risk of developing HF. It is associated with considerable morbidity and mortality, and accounts for approximately 1M hospitalizations annually; it is also a major cause of hospital readmission. The 2022 ACC/AHA Guideline for the Management of Heart Failure and 2021 update to 2017 ACC Expert Consensus Pathways for Heart Failure Treatment offers a comprehensive guide to treating this common condition. 

• Pathophysiology 
• Risk Factors 
• Diagnosis of HF 
• Workup at Time of Diagnosis 
• Key Points 
  • Terminology 
  • Stages and Classes of HF 
  • Treatment Considerations – GDMT 
  • HFpEF Management 
  • Dietary Recommendations Other Considerations 
• Learn More – Primary Sources 

Pathophysiology 

A cardiac insult (coronary artery disease, ischemia, hypertension, genetic cardiomyopathy, valvular disease, etc) will lead to left ventricular dysfunction and adverse remodeling which is further exacerbated by up-regulation of neurohormonal stimulation, endothelial dysfunction, vasoconstriction, and renal sodium retention causing signs and symptoms of heart failure. 

Risk Factors 

• Hypertension is the primary modifiable risk factor 
• Treating chronic hypertension leads to 50% reduction in risk of developing HF 
• Other risk factors 
  • Coronary artery disease (CAD) 
  • Diabetes 
  • Metabolic syndrome 
  • Smoking  
  • Alcohol  
  • Illicit drug use (cocaine, amphetamines) 
  • Obesity 
  • Genetic mutations that predispose to cardiomyopathies 
  • Family history of cardiomyopathy 

Diagnosis of HF 

• Primarily a clinical diagnosis utilizing history and physical exam 
• Cardinal symptoms 
  • Shortness of breath | Exercise intolerance | Fatigue | Edema 

Workup at Time of Diagnosis  

• Imaging 
  • Basic: EKG | Chest X-ray | Echocardiogram 
  • New HF with high suspicion for CAD: Coronary angiography or coronary CT angiography 
  • New HF with known CAD: Non-invasive imaging to detect myocardial ischemia (e.g. nuclear myocardial perfusion scan) or repeat invasive assessment. 
• Labs 
  • CBC | kidney and liver function | Electrolytes | Lipids | TSH | Urinalysis | BNP 
  • New evidence suggests screening BNP in patients at risk for HF (i.e. with ≥1 risk factors) “can be useful” in preventing clinical HF 

KEY POINTS: 

Terminology 

• Heart Failure with Reduced Ejection Fraction (HFrEF, LVEF ≤ 40 %) 
• Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF, LVEF 41-49%) 
• Heart Failure with Preserved Ejection Fraction (HFpEF, LVEF ≥ 50%) 

Stages and Classes of HF 

Guideline-directed medical therapy (GDMT) Is Tailored According to Severity of Disease 

• ACC/AHA stages of HF: Considers symptoms as well as structural cardiac abnormalities 
  • A: At risk for HF, no structural heart disease 
  • B: Structural heart disease, no symptoms of HF 
  • C: Structural heart disease with symptoms of HF 
  • D: Refractory HF (not responding to standard medical therapy) 
• New York Heart Association (NYHA) classes of HF: Subjective, based on symptomatology 
  • I: No limitation of physical activity 
  • II: Slight limitation of physical activity (OK at rest, symptomatic with “ordinary” activity) 
  • III: Marked limitation of physical activity (OK at rest, symptomatic with “less than ordinary” activity) 
  • IV: Symptomatic at rest or with any level of physical activity 

Treatment Considerations: 

Non-pharmacologic interventions: 

• Encourage healthy lifestyle habits such maintaining regular physical activity (adults should engage in at least 150 minutes/week of moderate intensity physical activity or 75 minutes/week of vigorous physical activity). 
• Avoid tobacco use and strongly encourage patients who smoke to quit. 

GDMT (Guideline-Directed Medical Therapy) 

• GDMT recommendations based on large RCTs showing morbidity and mortality benefit for Stages B-D HFrEF and HFmrEF only 
  • No mortality benefit in HFpEF 
• GDMT 
  • Reduces morbidity and mortality 
  • Improves symptoms and quality of life (QOL) 
  • Decreases hospitalizations 
• Some therapies limit cardiac remodeling and lead to improvements in ejection fraction (EF) over time 

ACE inhibitors (ACEI)/Angiotensin II receptor blockers (ARB): Associated with mortality benefit 

• Examples 
  • lisinopril, enalapril, fosinopril         
• Switch to ARB (losartan, valsartan) if chronic cough develops (20% of patients) with ACEI or can also initiate ARB from the start. 
• Reassess renal function and electrolytes within 1 to 2 weeks after initiation of ACEI or ARB 
• Do not combine ACEI and ARB 
• In NYHA class II to III patients tolerating ACEI/ARB, switch to Entresto (valsartan/sacubitril) 
  • Entresto should not be administered within 36 hours of the last dose of an ACEI 
  • If history of angioedema do NOT start Entresto 

Beta blockers:  Associated with mortality benefit 

• Examples 
  • Carvedilol | Bisoprolol | Metoprolol succinate (not tartrate) 
  • Titrate up to maximum tolerated dose 

Aldosterone antagonists: Mortality benefit for NYHA II-IV  

• Examples 
  • Spironolactone, eplerenone 
• Major risk is hyperkalemia 
  • Start only if GFR ≥ 30 ml/min/1.73 m2, creatinine  ≤ 2.5 mg/dl in males or  ≤ 2.0 mg/dl in female and potassium  ≤ 5 mEq/L 
  • Reassess renal function and electrolytes 3 and 7 days after starting, then check monthly for 3 months and every 3 months afterwards 
  • Ongoing area of research utilizing potassium binding agent (patiromer, sodium zirconium cyclosilicate) to minimize risk of hyperkalemia with aldosterone antagonists. 

Sodium-glucose cotransporter-2 inhibitor (SGLT2): Mortality benefit for NYHA II-IV  

• Empagliflozin for patients with GFR ≥ 20 ml/min/1.73 m2 or dapagliflozin for GFR ≥ 30 ml/min/1.73 m2 
• Can lower HgA1C by 0.6-0.9  
• Caution: increased risk of mycotic genital infections 
• May contribute to volume depletion; consider altering diuretic dosing accordingly 
• Necrotizing fasciitis of the perineum (Fournier’s gangrene): rare, serious, life-threatening manifested as pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. Educate patient on warning signs and symptoms. 

Loop diuretics: Indicated for Stages C-D for relief of symptoms due to fluid overload; no known effect on mortality 

• Examples 
  • Furosemide | Bumetanide | Torsemide 
• Titration 
  • Largely based on symptoms and clinical assessment of volume status (weight, urine output, BNP) 
  • Some patients will require chronic fixed doses to maintain euvolemia 

Other medications 

• Digoxin 
  • For persistent symptoms despite GDMT | Shown to decrease hospitalizations 
• Hydralazine + isosorbide dinitrate: For persistent symptoms despite GDMT in NYHA III-IV African American patients 
• Ivabridine 
  • Can reduce HF hospitalizations in a small subset of patients: NYHA class II-III with EF≤35% on GDMT and sinus rhythm with resting HR≥70 bpm 
  • Omega-3 fatty acids: “reasonable to use as adjunctive therapy” for NYHA II-IV HFrEF or HFpEF 

Drugs to avoid 

• Calcium channel blockers 
  • Can worsen HF (particularly non-dihydropyridines due to their negative inotropic effect); amlodipine may be OK 
• NSAIDs: Cause sodium and water retention 
• Thiazolidinediones: Increased incidence of HF events 

HFpEF Management 

• No pharmacological therapy has been found to decrease mortality. 
• If concomitant hypertension, titrate anti-hypertensives to blood pressure goal of <130/80 mmHg; first line ACEI or ARB 
• To decrease HF hospitalization, use SGTL2 inhibitors (empagliflozin) 
• Spironolactone and ARNi can also be used especially among patients with LVEF on lower end of spectrum (LVEF 50-55%). 
• For patients with persistent volume overload despite above, add diuretics. 

Dietary Recommendations 

• Sodium restriction 
  • Stages A and B: <1.5 g/day 
  • Stages C and D: <3 g/day 
• Fluid restriction: <1.5-2L/day only recommended in Stage D (refractory) HF 
• Emphasize healthy diet that emphasizes intake of vegetables, fruits, nuts, whole grains, lean vegetables, and fish. Minimize trans fats, red meat, processed red meats, refined carbohydrates, and sweetened beverages.  

Other Considerations 

• Indications for CABG 
  • HFrEF or HFpEF with angina despite GDMT or significant multivessel disease 
• Indications for Cardiac Resynchronization Therapy (CRT) to reduce total mortality, reduce hospitalization and improve symptoms/quality of life. 
  • EF≤35% (NYHA II-Ambulatory NYHA IV) with LBBB ≥ 150 msec or non-LBBB ≥ 150 msec 
  • On GDMT >3 months or >40 days after MI  
  • Expected survival ≥1 year 

• Indications for ICD placement for primary prevention of sudden cardiac death 
  • EF≤35% (NYHA II-III) or EF≤30% (NYHA I) 
  • On GDMT 
  • Expected survival ≥1 year 
• Repeat echocardiogram in a patient with ≥1 of the following 
  • Significant change in clinical status 
  • Experienced or recovered from a clinical event 
  • Received treatment, including GDMT, with potentially significant effect on cardiac function 
• HF and obstructive sleep apnea 
  • CPAP “can be beneficial” to improve functional status 
• HF and anemia 
  • NYHA II-III and iron deficiency (ferritin<100 ng/mL), IV iron can decrease HF hospitalization and improve functional status. 

Learn More – Primary Sources: 

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 

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