Heart Failure

• Heart failure (HF)


  A syndrome associated with signs and symptoms due to abnormalities in cardiac structure or function

  
• Heart failure

  • May be caused by an abnormality in systolic function, diastolic function, or both

  
• Heart failure with reduced ejection fraction (HFrEF)


  A clinical diagnosis of HF and an LVEF of 40% or less

  
• Heart failure with preserved EF (HFpEF)


  Defined as an LVEF of 50% or greater; borderline HFpEF is LVEF 41%–49%

  
• Causes of systolic dysfunction (decreased contractility)

  • Myocardial infarction

  
• Causes of diastolic dysfunction (restriction in ventricular filling)


  • Ventricular hypertrophy
  • Increased ventricular stiffness
• Leading causes of HF


  • Coronary artery disease
  • Hypertension

  
• Compensatory responses to maintain circulation with decreased cardiac output


  1. Tachycardia and increased contractility through sympathetic nervous system activation

  2. Increased preload (through sodium and water retention) increases stroke volume

  3. Vasoconstriction

  4. Ventricular hypertrophy and remodeling

  
• Chronic activation of the neurohormonal systems results in a cascade of events that affect the myocardium
• These events lead to changes in ventricular size (left ventricular hypertrophy), shape, structure, and function known as ventricular remodeling
• Primary symptoms of HF


  • Dyspnea
  • Fatigue
  • Edema
  • Exercise intolerance
• Goals of HF therapy

  • Modify or control risk factors (e.g., HTN, obesity, DM)
  • Manage structural heart disease
  • Reduce morbidity and mortality
  • Prevent or minimize Na and water retention
  • Eliminate or minimize HF symptoms
  • Block compensatory neurohormonal activation caused by reduced cardiac output (CO)
  • Slow progression of worsening cardiac function

  
• General approach to HFrEF pharmacologic therapy


  Initiation and titration of optimal medication therapy in HFrEF should prioritize angiotensin receptor-neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 (SGLT2) inhibitor use to reduce CV mortality and HF hospitalizations
• ACE inhibitors


  Recommended in all patients with HFrEF and current or prior symptoms when use with an ARNI is not feasible, unless contraindicated
• Benefits of ACE inhibitors


  • Decreased mortality (about 25%–50% relative risk reduction compared with placebo depending on severity of HF)
  • Decreased hospitalizations (about 30% relative risk reduction compared with placebo)
  • Symptom improvement
  • Improved clinical status
  • Improved sense of well-being
• Mechanism of action of ACE inhibitors


  • Blocks production of angiotensin II, decreasing sympathetic stimulation, aldosterone and vasopressin production, and vasoconstriction
  • Increases bradykinins, increasing vasodilatory prostaglandins and attenuating myocardial remodeling
• Angiotensin receptor blockers (ARBs)


  Recommended in patients with HFrEF with current or prior symptoms who are unable to take an ACE inhibitor or ARNI
• Benefits of ARBs


  • Decreased HF-related hospitalizations and decreased death from CV causes
• Mechanism of action of ARBs


  Selectively block the binding of angiotensin II to the angiotensin I receptor, deterring vasoconstriction and aldosterone-secreting effects
• Sacubitril/valsartan (ARNI)


  Recommended for patients with chronic HFrEF to reduce morbidity and mortality, and for patients with chronic symptomatic NYHA class II or III HFrEF who can tolerate an ACE inhibitor or ARB, to further reduce morbidity and mortality
• Benefits of sacubitril/valsartan


  • Decreased composite endpoint of death from CV causes or hospitalization for HF (20% relative risk reduction compared with enalapril monotherapy)
  • Decreased all-cause mortality (16% relative risk reduction) and CV death (20% relative risk reduction) compared with enalapril monotherapy
  • Decreased hospitalization for HF (21% relative risk reduction compared with enalapril monotherapy)
• Mechanism of action of sacubitril/valsartan


  • Sacubitril inhibits neprilysin, increasing levels of natriuretic peptides
  • Valsartan selectively blocks the angiotensin I receptor and inhibits angiotensin II–dependent aldosterone release
• β-blockers


  Recommended in all patients with HFrEF with current or prior symptoms unless contraindicated
• Benefits of β-blockers (when added to an ACE inhibitor)


  • Decreased mortality (about 35% relative risk reduction compared with placebo)
  • Decreased hospitalizations (about 25% relative risk reduction compared with placebo)
  • Symptom improvement
  • Improved clinical status
• Mechanism of action of β-blockers


  Blocks the effect of norepinephrine and other sympathetic neurotransmitters on the heart and vascular system, decreasing ventricular arrhythmias, cardiac hypertrophy and cell death, and vasoconstriction and HR
• Only bisoprolol, carvedilol, and metoprolol succinate are recommended in HFrEF
• Trials


  • CIBIS II (bisoprolol)
  • MERIT-HF (metoprolol succinate)
  • COPERNICUS (carvedilol)
  • COMET (metoprolol tartrate vs. carvedilol)
• Mechanism of action


  Blocks the effect of norepinephrine and other sympathetic neurotransmitters on the heart and vascular system
• Mechanism of action


  • Decreases ventricular arrhythmias (sudden cardiac death)
  • Decreases cardiac hypertrophy and cardiac cell death
  • Decreases vasoconstriction and HR

  
• Carvedilol


  • Provides α1 -blockade
  • Further decreases SVR (afterload)
  • Results in greater reduction in BP than metoprolol succinate
• Recommended β-blockers in HFrEF


  • Bisoprolol
  • Carvedilol
  • Metoprolol succinate
• Initiate β-blockers


  When HF symptoms are stable and patients are euvolemic
• β-blockers should not be prescribed without diuretics in patients with current or recent history of fluid retention
• Titrating β-blocker dose


  1. Start low and increase (double) the dose every 1– 2 weeks (or slower, if needed) to target dose

  2. Aim to achieve target dose in 8–12 weeks
• Avoid abrupt discontinuation of β-blockers as it can precipitate clinical deterioration
• Improvement in symptoms with β-blockers may not be noticed for several months
• β-blockers should be considered even in patients with reactive airway disease or asymptomatic bradycardia
• Recommended dosing for β-blockers


  • Bisoprolol
  • Carvedilol
  • Metoprolol succinate
• Mineralocorticoid receptor antagonists (MRAs)


  Recommended in patients with NYHA class II–IV with an LVEF of 35% or less to reduce morbidity and mortality unless a contraindication exists
• MRAs recommended after myocardial infarction


  In patients with an LVEF less than or equal to 40% with symptoms of HF or an LVEF less than 40% and DM