Therapy: Patients With Refractory End-Stage HF (Stage D)
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Overview of Stage D

Stage D
Refractory HF (heart failure) requiring specialized interventions
e.g., Patients who have marked symptoms at rest despite maximal medical therapy e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)
Therapy Goals
-  Appropriate measures under Stages A, B, C
-  Decision re: appropriate level of care
-  Compassionate end-of-life care/hospice
-  Extraordinary measures
-  heart transplant
-  chronic inotropes
-  permanent mechanical support
-  experimental surgery or drugs

Summary of therapy options -  Stage D

Patients With Refractory End-Stage HF (Stage D)

Before a patient is considered to have refractory HF, physicians should confirm the accuracy of the diagnosis, identify any contributing conditions, and ensure that all conventional medical strategies have been optimally employed. Measures listed as Class I recommendations for patients in stages A, B, and C are also appropriate for patients in end-stage HF . When no further therapies are appropriate, careful discussion of the prognosis and options for end-of-life care should be initiated.


Class I 

1. Meticulous identification and control of fluid retention is recommended in patients with refractory end-stage HF. (Level of Evidence: B)

2. Referral for cardiac transplantation in potentially eligible patients is recommended for patients with refractory end-stage HF. (Level of Evidence: B)

3. Referral of patients with refractory end-stage HF to an HF program with expertise in the management of refractory HF is useful. (Level of Evidence: A)

4. Options for end-of-life care should be discussed with the patient and family when severe symptoms in patients with refractory end-stage HF persist despite application of all recommended therapies. (Level of Evidence: C)

5. Patients with refractory end-stage HF and implantable defibrillators should receive information about the option to inactivate defibrillation. (Level of Evidence: C)

Class IIa

1. Consideration of an LV assist device as permanent or ?destination? therapy is reasonable in highly selected patients with refractory end-stage HF and an estimated 1-year mortality over 50% with medical therapy. (Level of Evidence: B)

Class IIb

1. Pulmonary artery catheter placement may be reasonable to guide therapy in patients with refractory end-stage HF and persistently severe symptoms. (Level of Evidence: C)

2. The effectiveness of mitral valve repair or replacement is not established for severe secondary mitral regurgitation in refractory HF. (Level of Evidence: C)

3. Continuous intravenous infusion of a positive inotropic agent may be considered for palliation of symptoms in patients with refractory end-stage HF. (Level of Evidence: C)

Class III

1. Partial left ventriculectomy is not recommended in patients with nonischemic cardiomyopathy and refractory end-stage HF. (Level of Evidence: C)

2. Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF. (Level of Evidence: B)

End-of-Life Considerations - Recommendations  

Class I 

1. Ongoing patient and family education regarding prognosis for functional capacity and survival is recommended for patients with HF at the end of life. (Level of Evidence: C)

2. Patient and family education about options for formulating and implementing advance directives and the role of palliative and hospice care services with re-evaluation for changing clinical status is recommended for patients with HF at the end of life. (Level of Evidence: C)

3. Discussion is recommended regarding the option of inactivating an implanted cardioverterdefibrillator for patients with HF at the end of life. (Level of Evidence: C)

4. It is important to ensure continuity of medical care between inpatient and outpatient settings for patients with HF at the end of life. (Level of Evidence: C)

5. Components of hospice care that are appropriate to the relief of suffering, including opiates, are recommended and do not preclude the options for use of inotropes and intravenous diuretics for symptom palliation for patients with HF at the end of life. (Level of Evidence: C)

6. All professionals working with HF patients should examine current end-of-life processes and work toward improvement in approaches to palliation and end-of-life care. (Level of Evidence: C)

Class III 

1. Aggressive procedures performed within the final days of life (including intubation and implantation of a cardioverter-defibrillator in patients with New York Heart Association functional class IV symptoms who are not anticipated to experience clinical improvement from available treatments) are not appropriate. (Level of Evidence: C)

Oral Diuretics Recommended for Use in the Treatment of Chronic Heart Failure

Drug Initial Daily Dose(s) Maximum Total Daily Dose Duration of action
Loop Diuretics
Bumetanide Oral: 0.5 to 1 mg qd-bid 10 mg 4 to 6 hours
Furosemide Oral: 20 to 40 mg qd-bid 600 mg 6 to 8 hours
Torsemide Oral: 10 to 20 mg qd 200 mg 12 to 16 hours
Thiazide Diuretics
Chlorthiazide 250-500 mg qd-bid 1000 mg 6 to 12 hours
Chlorthalidone 12.5 to 25 mg qd 100 mg 24 to 72 hours
Hydrochlorothiazide 25 mg qd - bid 200 mg 6 to 12 hours
Indapamide 2.5 mg qd 5 mg 36 hours
Metolazone 2.5 mg qd 20 mg 12 to 24 hours
Potassium-sparing diuretics
Amiloride 5 mg qd 20 mg 24 hours
Spironolactone 12.5 to 25 mg qd 50 mg (possibly higher doses in select cases) 2 to 3 days
Triamterene 50 to 75 mg bid 200 mg 7 to 9 hours
Sequential Nephron blockade
Metolazone 2.5 to 10 mg qd plus loop diuretic
Hydrochlorothiazide 25 to 100 mg qd-bid plus loop diuretic
Chlorthiazide (IV) 500 to 1000 mg qd plus loop diuretic
Intravenous Diuretic Medications Useful for the Treatment of Severe Heart Failure
Loop Diuretics
Drug Initial dose Max single dose  
Bumetanide 1 mg 4 to 8 mg  
Furosemide 40 mg 160 to 200 mg  
Torsemide 10 mg 100 to 200 mg  
Thiazide Diuretics
Chlorthiazide 500mg 1000 mg  
Intravenous Infusions
Bumetanide 1 mg IV load, then 0.5 to 2 mg per hour
Furosemide 40 mg IV load, then 10 to 40 mg per hour
Torsemide 20 mg IV load, then 5 to 20 mg per hour

Medications Commonly Used for the Treatment of Patients with Heart Failure with Low Ejection Fraction
Drug Initial Daily Dose(s) Maximum Dose(s)
Captopril 6.25 mg tid 50mg tid
Enalapril 2.5 mg bid 10 to 20 mg bid
Fosinopril 5 to 10mg qd 40mg qd
Lisinopril 2.5 to 5 mg qd 20 to 40 mg qd
Perindopril 2 mg qd 8 to 16 mg qd
Quinapril 5 mg bid 20 mg bid
Ramipril 1.25 to 2.5 mg qd 10mg qd
Trandolapril 1 mg qd 4 mg qd
Angiotensin Receptor Blockers
Candesartan 4 to 8 mg qd 32 mg qd
Losartan 25 to 50 mg qd 50 to 100 mg qd
Valsartan 20 to 40 mg bid 160 mg bid
Aldosterone Antagonists
Spironolactone 12.5 to 25 mg qd 25 mg qd to bid
Eplerenone 25 mg qd 50 mg qd
Bisprolol 1.25 mg qd 10 mg qd
Carvedilol 3.125 mg bid 25 mg bid. 50mg bid for patients > 85 kg.
Metoprolol succinate extended release 12.5 to 25 mg qd 200mg qd


Direct quotes from this valuable reference:
Hunt SA, Abraham WT, Chin MH, Feldman AM, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005 Sep 20;112(12):e154-235. Epub 2005.  
Link: http://circ.ahajournals.org/cgi/content/full/112/12/e154


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