End-stage (Refractory) Heart Failure

Background

• End-stage heart failure refers to progression of heart failure despite optimal guideline-directed medical, surgical, and device therapy.
• Most patients with end-stage heart failure have heart failure with reduced ejection fraction (HFrEF), but patients with heart failure with preserved ejection fraction (HFpEF) may also develop end-stage heart failure.
• Classification of heart failure varies among different professional organizations.

Evaluation

• Recognition of end-stage heart failure is challenging in patients with progressive heart failure as signs and symptoms are usually chronic, insidious, and nonspecific, however there are a number of clinical events and findings suggestive of end-stage heart failure.
• Consider the following blood test abnormalities in support of a diagnosis of end-stage heart failure:
  • elevated B-type natriuretic peptide (BNP) despite guideline-directed maximally tolerated medical therapy
  • persistent hyponatremia (serum sodium ≤ 134 mEq/dL)
  • rise in blood urea nitrogen and creatinine indicating progressive renal and other organ dysfunction
• Consider cardiopulmonary exercise testing:
  • 6-minute walking test findings suggesting end-stage heart failure with poor prognosis include
    • peak oxygen consumption (VO₂) of ≤ 10-12 mL/kg/minute
    • walking distance < 300 meters
• Other markers suggestive of end-stage heart failure:
  • need for IV inotropic therapy for symptom relief or to maintain end-organ function
  • ≥ 2 heart failure admissions in the past 12 months
  • > 2 unscheduled visits (such to the emergency department or clinic) in the past 12 months
  • diuretic refractoriness associated with worsening renal function
  • inability to tolerate neurohormonal antagonists (circulatory-renal limitation to renin-angiotensin-aldosterone system inhibition or beta-blocker therapy)
  • recurrent refractory ventricular tachyarrhythmias; frequent implantable cardioverter-defibrillator shocks
  • cardiac cachexia
  • progressive/persistent New York Heart Association (NYHA) class III-IV symptoms and inability to perform activities of daily living
• Consider right heart catheterization, which may help identify patients who may require inotropic support as bridge to mechanical circulatory support, transplantation, or palliative care.
• Consider testing to determine extent and reversibility of complications in selected organs:
  • consider determining reversibility of pulmonary hypertension if present
  • if cardiac transplant or left ventricular assist device is being considered, liver biopsy may be used to determine extent of irreversible liver injury and surgical options

Management

• The care team should include a heart failure specialist, a cardiothoracic surgeon, and a palliative care specialist.
• The care plan should include a discussion with patient of their:
  • prognosis
  • treatment goals (such as preference for survival vs. quality of life)
  • available treatment options
• Available treatment options include:
  • IV inotropic support
  • mechanical circulatory support (MCS) (including left ventricular assist devices)
  • cardiac transplantation
  • palliative and hospice care
• Decisions about treatment options should be based on providing the patient with a clear understanding of the balance of risk and benefit for each option and incorporation of patient preferences.