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INTRODUCTION

Quick Look

• Heart failure with left ventricular systolic dysfunction (LVEF <40-45%).
• Heart failure with left ventricular diastolic dysfunction (LVEF >40-45%). Other terminology for this diagnosis is
• heart failure with preserved left ventricular systolic function.
• Coronary artery disease and systemic hypertension are the two most common conditions leading to heart failure.
• Treatment of asymptomatic left ventricular systolic dysfunction is as important as treatment of symptomatic condition.

Adequate evaluation for:

• Non-cardiac causes of heart failure such as, anemia, abnormal thyroid function, etc.
• Potential reversible cardiac causes of heart failure such as myocardial ischemia, valvular heart disease, etc.
• Other causes of symptoms mimicking heart failure such as primary pulmonary conditions, other causes of edema.
• Left ventricular systolic vs left ventricular diastolic dysfunction.

Adequate treatment of:

• Conditions aggravating or leading to heart failure such as systemic hypertension, coronary disease, acute myocardial infarction, valvular disease, arrhythmia, sleep apnea, etc.

Adequate prevention of:

• Conditions aggravating or precipitating heart failure such as: modifying cardiac risk factors for coronary disease; providing immunization for influenza and pneumococcal pneumonia.

Education needs to include several components:

• Understanding the heart failure condition; how heart failure is managed; the patient's responsibility; daily weighing; salt restriction; the importance of compliance; the reward of exercise; etc.
• Involve the patient's family.
• Education points should be reinforced and the patient's understanding should be evaluated.
• Education process is more effectively performed by non-physician personnel, such as a trained nurse.

Pharmacological management. (more detail in Pharmacological Management Section)

• Poly-pharmacy approach.
• Medications that have the effect on the natural history of the disease, especially the neurohormonal antagonist (ACE inhibitors, beta blockers, aldosterone antagonist and angiotensin receptor blocker) should be part of the treatment strategy.
• Prescribe only the medications that have proven benefit and use the appropriate dose used in major clinical trials.
• Start each medication at appropriate level of NYHA class and dosage.
• Be aware of medications adverse reactions and how to manage them.
• Avoid prescribing medications that potentially have deleterious effects in heart failure with left ventricular systolic function such as most of the calcium channel blockers, antiarrhythmic class 1A, 1C, NSAIDs, Cox 2 inhibitors and Glitazones (in heart failure with fluid retention).
• Encourage prescribing aspirin, beta blockers, ACE inhibitors and statin drugs in post MI patients.
  
  ACE inhibitors (ACEIs)
  • Benefit through neurohormonal antagonist mechanism to delay the disease progression and improve mortality.
  • Should prescribe in all patient with systolic dysfunction as the first medicine.
  • Appears to have class effect. There is no direct comparison between "Tissue" and "Non tissue" ACEIs. FDA has approved 7 ACEIs for heart failure treatment.
  • Currently ACEIs are the only medicine recommended in asymptomatic left ventricular systolic dysfunction.
  • Initiating and target dose for heart failure and for stable hypertension treatment may be different. Starting dose of ACEIs for heart failure treatment is usually lower. Target dose for hypertension treatment is usually as needed, up to maximal dose.
  • Try hard to prescribe this important medicine and raise to target dose (dose used in clinical trials). Prescribe them at lower dose (because of adverse reaction at higher dose) is better than not prescribing them (ATLAS trial for lisinopril)
  • Awareness of relationship of ACEIs, diuretics, and beta blockers.
  • Know how to manage ACEIs adverse reactions and renal insuffeciency.

  Beta blockers

  • Another neurohormonal antagonist to delay the disease progression and improving mortality.
  • Should prescribe in heart failure patient with systolic dysfunction in NYHA class (I) II - IV.
  • Usually prescribe after ACEI. Avoid starting in an unstable patient.
  • Have not been proven to have class effect. Only 3 beta blockers have proven mortality benefit. FDA has approved 2 beta blockers for heart failure treatment.
  • Initiating and target dose for heart failure and for other indications may be different.
  • Try hard to prescribe this important medicine and raise to target dose (dose used in clinical trials) Prescribe them at lower dose (because of adverse reaction at higher dose) is better than not prescribing them at al (MOCHA trial for Carvedilol).
  • Should always prescribe in post MI patients with or without heart failure. Beta blockers in post MI trials are not the same as in heart failure trials.

  Aldosterone antagonist

  • New neurohormonal antagonist to improve heart failure mortality.
  • The RALES trial Aldactone only includes patients in NYHA class IV and if they are in class III, they were in class IV within 6 months.
  • The EPHESUS trial for Eplerenone includes patients with recent MI, heart failure and EF of 40% or less.
  • Creatinine and potassium level should be <2.5 mg/dl and <5.0 mEq/L.

  Angiotensin receptor blocker (ARBs)

  • Prescribe to heart failure (HF) patients who cannot take ACEI.
  • There are conflicting data when add ARB to ACEI or to ACEI and Beta Blocker.
    1. VAL-HeFT Trial, 2001. Benefit when add to ACEI, but no benefit when add ARB to ACEI and Beta blocker.
    2. CHARM Trial, 2003. Add benefit when add ARB to ACEI or add ARB to ACEI and beta blocker (Triple therapy).
    3. VALIANT Trial, 2003. No benefit when add ARB to ACEI in early post MI patients.

    Comment: (1) CHARM trial result is considered more accurated than VAL-HeFT trial in regarding combine ACEI and ARB. (2) VALIANT patient population is different from CHARM and VAL-HeFT trial. (3). Benefit in heart failure with preserved LV systolic function (CHARM 2003).

  Digitalis

  • Indicated for improving symptoms in patients who are already on ACEI, beta blocker and diuretic. It does not effect progression of the disease.

  Diuretics

  • Remain essential for symptomatic relief of fluid retention.

  Hydralazine

  • Prescribe in combination with isosorbide dinitrate (ISDN) to patients who cannot tolerate or who are contraindicated to ACEIs or ARBs.
  • No proven benefit if prescribing Hydrazine or ISDN alone.
  • Hydralazine blocks the development of nitrate tolerance.
  • Hydralazine is an antioxidant.

  Calcium channel blockers

  • They have deleterious effect on left ventricular systolic function and worsening of heart failure, except for amlodipine (norvasc), and felodipine (plendil).

  Anticoagulation (chronic)

  • Warfarin is indicated in heart failure patients with atrial fibrillation, history of systemic emboli or other usual indications for long term use of anticoagulation.
  • No uniform recommendation prescribing warfarin in patients with EF <30%.

  ASA

  • ASA-ACEI interaction through prostaglandin synthesis has not been resolved.
  • Current recommendation is to continue the use of ASA and ACEI for their indications as usual.
  • Lower ASA dose (<100 mg/day) may inhibits thromboxane production while preserving prostacyclin formation.
  • Fortunately current recommending ASA dose for ischemic heart disease is 81 mg/day based on effectiveness and less GI side effect.
  • Antiplatelet agents that do not interfere with prostaglandin synthesis such as ADP antagonist (Ticlopidine, Clopidogrel) can be substituted for ASA if there is evedence of ASA intolerance.

  Antiarrhythmics

  • Only amiodarone, beta blockers and dofetilide (tikosyn) do not have deleterious effect on left ventricular systolic function.

  IV inotropes

  • Prescribe for enhancing diuresis in diuretic refractory patients or severe NYHA class IV patients or patients waiting for transplantation.
  • There is no definite proven benefit for out patient or intermittent use of these agents.

  Medicines worsening/exacerbate heart failure

  • NSAIDs, Cox 2 inhibitors, class I antiarrhythmic agents, calcium channel blockers except amlodipine and felodipine, corticosteroid, lithium, tricyclic antidepressants, cardiotoxic agents, glitazones (in HF with fluid retention).

  
  BNP ( B-type Natriuretic Peptide)

  • New development in heart failure diagnosis and treatment

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Heart Failure Classification

ACC/AHA, 2001		NYHA
A	At high risk of developing HF, but without structural heart disease or symptoms of HF	None	.
B	Structural heart disease, but without symptoms of HF	I	Asymptomatic
C	Structural heart disease with prior or current symptoms of HF	II	Symptomatic with moderate exertion
		III	Symptomatic with minimal exertion
		IV	Symptomatic at rest
		IV
D	Refractory HF requiring specialized interventions

ACC = American College of Cardiology.
AHA = Americal Heart Association.
NYHA = New York Heart Association.
HF = Heart Failure

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Medicines and when should they be prescribed

MEDICINES	INDICATION	Improve Symptoms	Decrease Hosp	Decrease Mortality
ACE Inhibitor	- NYHA I - IV - Only medicine proved benefit in NYHA I. - First medicine to start.	Y	Y	Y
Beta Blocker	- NYHA II - IV - Do not start in unstable patients. - Should start early but not before ACEI.	Y	Y	Y
Aldosterone Antagonist	- NYHA (III) IV in RALES study (Spironolactone) - Recent MI with heart failure in EPHESUS study (Eplerenone)	Y	Y	Y
Angiotensin II Receptor Blocker	- Substitute for patients that cannot use ACEI. - Benefit when add to ACEI, or add to ACEI and beta blocker (and aldosterone) (CHARM, 2003)	a	a	a
Hydralazine+ISDN	- Substitute for patients that cannot use ACEI and ARB.	Y	.	Y
Diuretic	- NYHA II - IV - For symptomatic patients with fluid retention.	Y	Y	b
Digitalis	- NYHA II -III (IV) - For symptomatic patients already on ACEI, beta blocker and diuretic.	Y	Y	.
Antiarrhythmic Agent	- Amiodarone, (some) beta blocker, and dofetilide do not have negative effect on HF patients.	.	.	.
Anticoagulation	- No conclusive recommendation for patients with EF <30%. - Usual indications i.e.., atrial fibrillation, history of systemic emboli.	.	.	.
Calcium Channel Blocker	- No indication for heart failure treatment. - Only amlodipine and felodipine do not has deleterious effect on depressed LV function.	.	.	.
Medicines not recommend	- NSAIDs, Cox 2 inhibitors, Class 1A and 1C antiarrhythmic agents , calcium channel blocker except amlodipine and felodipine, glitazones (avandia and actose in Heart failure with fluid retention, cardiotoxic agents. -Others include coticosteroid, lithium, tricyclic antidepressants.

a = Appears to have similar result and not better than ACEI.
b = No confirmed data to date.

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Medicines and when should they be prescribed. A Quick Reference

.	I	II	III		IV
IV Inotropic	.				.
Digitalis	.	.			1
Diuretic	.	.
Aldosterone antagonist	.			2
Beta blocker	3	4
ARB	5
ACE Inhibitor	.

1. Digitalis should not be started during this NYHA class.   2. Spironolactone adds to ACEI, Beta blocker (RALES Trial). May prescribe Eplerenone soon after MI with heart failure (EPHESUS Trial).  3. Prescribe after acute MI with or without heart failure symptoms.   4. Add to ACEI. Do not have to wait until reach ACEI target dose.   5a. Prescribe when patient is intolerable or contraindicate to ACEI.   5b. Add to ACEI, Beta blocker. (CHARM, 2003)

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ACC/AHA Stages, Progression, and Treatment of HF, 2001

This new HF staging also includes incorporation of conditions which potentially leading to HF and cardiac structural abnormality, which should lead to more appropriate management to slow down the progression of disease and improvement of quality of life.

Stage A - At high risk for developing of HF but without structural heart disease or symptom of HF.	.	Stage B - Structural heart disease but without symptoms of HF.	.	Stage C - Structural heart disease with prior or current symptoms of HF.	.	Stage D - Refractory HF required specialized interventions.
.	.	.	.	.	.	.
e.g.. Patients with: - Hypertension, coronary artery disease, diabetes mellitus, using cardiotoxins, FH of CM.	.	e.g.. Patients with: - previous MI, Left ventricular systolic dysfunction, asymptomatic valvular disease.	.	e.g.., Patients with: - known structural heart disease, shortness of breath and fatigue, reduced exercise tolerance.	.	e.g.., Patients who: - have marked symptom 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: - Treat hypertension, encourage smoking cessation, treat lipid disorders, encourage regular exercise, discourage alcohol intake, - ACEI in atherosclerotic vascular disease of diabetic patients.	.	Therapy: - All measures under Stage A. - Heart failure education. - ACEI and Beta blocker S/P MI patients regardless of EF. - ACEI in low EF patients regardless of MI history. - Beta blocker in symptomatic low EF regardless of MI history. - ICD in appropriate patients.	.	Therapy: - All measures under Stage A. - Extensive heart failure education. - Drugs for routine used: ACEI, beta blocker, diuretic, digitalis, spironolactone,ARB, hydralazine and nitrate, etc. - ICD/biventricular pacing in appropriate patients.	.	Therapy: - All measures under Stage A, B, and C. - Mechanical assist devices. - Heart transplantation. - Continuous (not intermittent) IV inotropic infusion for palliation. - Hospice care.

HF = Heart Failure, FH = Family History, CM = Cardiomyopathy, S/P = Status Post, MI = Myocardial Infarction,
ACEI = Angiotensin Converting Enzyme Inhibitor, ARB = Angiotensin Receptor Blocker.

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