Congestive heart failure treatment of patients with current or prior symptoms of heart failure (Stage C)

Overview
Several measures have been listed for patients in Stage A or B as previously mentioned and the Class 1 recommendations for those patients are also appropriate for patients with current or previous symptoms of HF. The effectiveness of diuretics and safety of their usage is an important aspect of the treatment that should be closely monitored along with daily measurement of weight and moderate sodium restriction. Physical activity is highly recommended, although heavy labor or sports shouldn’t be a part of it. A reduction in physical activity promotes physical deconditioning, and an increase of weight which may be associated with more strain on the failing heart. Patients with chronic conditions such as HF are also recommended to be immunized with influenza and pneumococcal vaccines in order to reduce the risk of respiratory infection.

Drugs that should be avoided or used with caution in patients with HF
Pharmacological therapy should be closely monitored and several classes of drugs should be avoided in case of HF:


 * Calcium Channel blockers: There is no direct role of these drugs in the management of HF, due to negative and possible deleterious effect in patients with HF due to systolic dysfunction . Vasoelective Calcium Channel blockers as amlodipine and felodipine have not been linked to adverse effect in HF treatment, but there is no evidence of efficacy for these drugs in the management of HF. However, amlodipine and felodipine appear to be safe for the treatment of concomitant disease in HF patients, such as angina or hypertension.

Amiodarone is considered the safest of the antiarrhythmic drugs because of its minimal proarrhythmic effect and is generally the preferred drug for treating arrhythmias in HF patients.
 * Antiarrhythmic agents: Negative inotropic effect exerted by most antiarrhythmic drugs can precipitate HF in patients with reduced LV function. The reduction in LV function can also reduce the elimination of these drugs leading to further drug toxicity. Other antiarrhythmic drugs can induce some proarrhythmic effect, especially class 1 agents and class 3 agents Ibutilide and sotalol; the same class 3 agents in addition to dofetilide can induce torsades to pointes.


 * Nonsteroidal anti-inflammatory drugs (NSAID): The administration of non-selective NSAIDs in HF patients is linked with an increased risk of HF exacerbation, increased renal dysfunction, and abnormal responses to ACEIs and diuretics. COX-2 selective inhibitors have not been fully investigated, but observational studies indicate that they may be linked with an increased rate of HF exacerbation and increased mortality.

Aspirin benefits and risks are not well established in patients with HF and Vascular disease (includingCAD). The potential interaction between ACEIs and beta blockers is of great importance. Although no data has proven that aspirin causes more frequent HF exacerbations and interactions with those drugs, health care providers should be aware of the possibility of such risks, but no recommendation for or against aspirin therapy in patients with heart failure can be made before further data are available.

Metformin - one of the most common side effects of metformin is lactic acidosis, which can be fatal in patients with HF.
 * Oral Hypoglycemic agents: two oral hypoglycemic agents, metformin and thiazolidinediones are considered to be risky in patients with HF.

Thiazolidinediones - the biggest risk of using Thiazolidinediones is fluid retention which may cause severe worsening of patients with HF.


 * Antidepressants: Depression is a common finding between patients suffering from HF that is usually related to high mortality rate and bad prognosis of those patients. Limited data are available on the safety and the risks associated with the usage of antidepressants in patients with heart failure. Health care providers should be aware of major cardiovascular events (as HF, MI, Stroke, cardiovascular death ) that is associated with Tricyclic antidepressants (TCAs) and Selective serotonin reuptake inhibitors (SSRIs).


 * Phosphodiesterase inhibitors PDE – The PDE-3 inhibitors as Cilostazol and PDE-4 as Anagrelide should be avoided in patients with HF, because of an increase risk of high-output heart failure and fluid retention that is associated with those drugs.

PDE-5 inhibitors such as sildenafil, vardenafil, and tadalafil, are widely used in the management of erectile dysfunction in men. The use of those agents with any form of nitrate therapy is contraindicated because of severe hypotensive effect that can be life threatening. In a trial where sildenafil and placebo were randomly assigned to 34 HF patients, no significant difference of symptomatic hypotension was observed, but HF patients with borderline low blood pressure and/or low volume status are in risk of severe hypotension and should avoid any PDE-5 inhibitors use.


 * Chemotherapy – Cardiotoxic chemotherapeutic agents as Cyclophosphamide, Trastuzumab, Bevacizumab and Anthracyclines, should be avoided in HF patients


 * Tumor Necrosis Factor alpha inhibitors TNF-alpha: New onset or worsening of pre-existing heart failure have been linked to TNF-alpha inhibitors. Infliximab has been specifically contraindicated in doses over 5mg/kg in patients with heart failure.


 * Antihistamines: some second generation antihistamines as terfenadine and astemizole have been reported to cause long QT syndrome and should not be used in HF patients.

Serum potassium should be closely monitored in HF patients, in order of preventing either hypokalemia or hyperkalemia, which could greatly affect cardiac excitability and conduction, leading to sudden cardiac death. Serum potassium should be maintained between 4.0 to 5.0 mEq per liter range, because low potassium level may affect digitalis and antiarrhythmic drugs treatment, while high potassium level can prevent the use of treatments known to prolong life.

Supervision of HF patients with close monitoring of treatment and diet is a very important aspect of the follow-up process in those individuals. Body weight and medications should be closely monitored, because any minor change in those parameters can have a significant effect over symptoms and hospitalization of patients with HF. Patient education is a crucial aspect of the management of HF, patient and family surveillance over any new change of symptoms or body weight is important in allowing early detection of those changes and implementing new treatment strategies to reduce further complications.

Pharmacological Therapy of HF
Improving symptoms, reducing mortality and slowing or reversing myocardial deterioration are the main goals of pharmacological therapy in HF patients. The therapy should be also directed at preventing arrhythmias, embolic events and other exacerbating factors. Different strategies have been implemented in the treatment of HF, but the ACC/AHA recommendations are based on a combination of 3 types of drugs: a Diuretic, an ACEI or an ARB, and a beta blocker. A review of data from several trials, provide clear evidence supporting the central role of these drugs in HF patient Therapy. The Diuretics play an important role in controlling fluid retention and achieving a euvolemic state. On the other hand, ACEI and a beta blocker should be started and maintained in patients who can tolerate them because of their major effect in controlling symptoms and reducing mortality. Digoxin can be added to this regime as a fourth agent to reduce symptoms, reduce recurrent hospitalization, control great and rhythm, and enhance exercise tolerance.

Diuretics
Different classes of diuretics have been implicated in the treatment of CHF. Loop Diuretics such as furosemide, bumetanide and torsemide, act on the inhibition of sodium and chloride reabsorption in the loop of Henle, whereas thiazide diuretics, metolazone, and potassium sparing diuretics as spironolactone act on the distal portion of the renal tubule. Loop diuretics increase sodium secretion up to 25 % of the filtered load of sodium, enhance free water clearance and maintain their efficacy unless severe renal impairment is present. Thiazide diuretics in contrast, increase the fractional excretion of sodium to a maximum of 10% of the filtered load, decrease free water clearance and lose their efficacy in patients with impaired renal function. For such reasons, loop diuretics are much preferred, unless hypertension with mild fluid retention is present in HF patients, where thiazide diuretics may have a better antihypertensive effect in this case.

Different short-studies demonstrated the efficacy of diuretics in improving various symptoms of HF, reducing jugular venous pressure, pulmonary congestion, peripheral edema and body weight, all within days of initiation of therapy. No long term studies have been conducted so far to reveal the effects of diuretic therapy on morbidity and mortality, but an improvement in cardiac function and exercise tolerance in patients with HF have been demonstrated in intermediate-term trials.

Diuretics produce great symptomatic benefits, much more rapidly than any other drugs for HF, they can adequately control the fluid retention of HF, relieving pulmonary edema and peripheral edema within hours or days. However, Diuretics should not be used alone in controlling Stage C HF. They should be combined with an ACEI and a beta blocker to avoid further clinical deterioration and maintain the HF symptoms under control.

Appropriate dose of diuretics should used in treatment of HF, because low doses will cause fluid retention, which can lead to a reduced response to ACEIs and ARBs and an increase risk of decompensation with the use of beta blockers, while excessive diuretics will lead to volume contraction which can increase the risk of hypotension and renal insufficiency with ACEIs, ARBs and beta blockers.

Loop diuretics are usually the first diuretics to be used to control pulmonary and/or peripheral edema. Furosemide is the most commonly used, but some patients may respond favorably to other agents in this category (as torsemide and Bumetanide) because of superior absorption and longer time of action.

The starting dosage is usually 20 to 40 mg of furosemide or its equivalent, but the exact dosing should always be monitored according to diuresis and other clinical symptoms, since the ultimate goal is to eliminate the evidence of fluid retention such as jugular venous pressure elevation and peripheral edema. Outpatients with HF are usually started with low dose until urine increases and weigh decreases by 0.5 to 1.0 kg daily. Diuretic therapy should be also combined with moderate dietary sodium restriction. Unstable or severe disease, should be controlled with intravenous diuretics( bolus or continuous infusion) and thiazide diuretics can be added for a synergistic effect.

Reducing overall volume may decrease intracardiac filling pressure resulting in a lower cardiac output via the Frank-Starling relationship. This effect is usually a minor effect and does not alter the course of the therapy. On the other hand, an unexplained increase in BUN and creatinine should be closely monitored and suspected as a sign of abnormal tissue perfusion. In this case renal function and other end organ perfusion should be assessed to avoid any concomitant complications.

Angiotensin Converting Enzyme Inhibitors
Patients with moderate to severe HF or asymptomatic left ventricular dysfunction show a great improvement in survival rate with the usage of ACE inhibitors. ACE inhibitors enhance the action of kinins and augment kinin-mediated prostaglandin production, so the effect of ACEIs cannot be solely explained by the suppression of Angiotensin II production. Furthermore, it has been proven that ACEIs modify cardiac remodeling more favorably than ARBs in experimental models of HF. Several studies indicates that ACEIs can alleviate symptoms, improve clinical status and sense of well being in patients with HF.

Another important aspect of ACEIs therapy is the reduction of mortality and hospitalization in such patients. These benefits were noticed in patients with mild, moderate or even severe symptoms of HF, with or without CAD. In general ACEIs should be used together with a beta blocker and should not be used without diuretics in patients with a current or recent history of fluid retention, because of the important role of diuretics in maintaining sodium balance and preventing the development of peripheral and pulmonary edema.

For the reasons mentioned above, ACEI therapy should be started in asymptomatic or symptomatic patients with HF. The beginning therapy should be a low dose ( eg, 2.5 mg of enalapril twice a day, 6.25 mg of captopril three time a day or 5 mg of lisinopril once a day). The dose should be gradually increased in one to two week if the initial therapy is tolerated and try to target a dose of 20 mg of enalapril twice a day, or 50 mg of captopril three times a day or up to 40 mg of lisinopril a day. Plasma potassium and renal function should be assessed one to two weeks after starting or changing a dose and periodically thereafter. Physicians should attempt to target certain doses which have been proved to reduce the risk of cardiovascular events. If these target doses of ACEIs cannot be used or poorly tolerated than intermediate doses should be implemented.

NSAIDs should be avoided since they may cause an increase in adverse effects of ACEIs in patients with HF and a decrease in the favorable effect of ACEIs therapy. Some evidence suggests that aspirin may inhibit the acute hemodynamic benefits of ACEIs. If the patient has a know history of coronary artery disease(CAD) then use of ASA along with ACEIs is recommended. However, but in patients with no history of CAD, there is no evidence to support the use of aspirin.

Overview of Treatment of Patients With Current or Prior Symptoms of Heart Failure (Stage C)
==ACC / AHA Guidelines- Patients with Reduced LVEF (DO NOT EDIT) == {{cquote|

Class I
1. Measures listed as Class I recommendations for patients in stages A and B are also appropriate for patients in Stage C. (Levels of Evidence: A, B, and C as appropriate)

2. Diuretics and salt restriction are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention. (Level of Evidence: C)

3. Angiotensin converting enzyme inhibitors are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. (Level of Evidence: A)

4. Beta-blockers (using 1 of the 3 proven to reduce mortality, i.e., bisoprolol, carvedilol, and sustained release metoprolol succinate) are recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. (Level of Evidence: A)

5. Angiotensin II receptor blockers approved for the treatment of HF are recommended in patients with current or prior symptoms of HF and reduced LVEF who are ACEI-intolerant (as in patients with angioedema). (Level of Evidence: A)

6. Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HF and reduced LVEF should be avoided or withdrawn whenever possible (e.g., non steroidal anti-inflammatory drugs, most antiarrhythmic drugs, and most calcium channel blocking drugs; see text). (Level of Evidence: B)

7. Exercise training is beneficial as an adjunctive approach to improve clinical status in ambulatory patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: B)

8. An implantable cardioverter-defibrillator is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. (Level of Evidence: A)

9. Implantable cardioverter-defibrillator therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-MI, have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: A)

10. Implantable cardioverter-defibrillator therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with non ischemic cardiomyopathy who have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: B)

11. Patients with LVEF less than or equal to 35%, sinus rhythm, and NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than 0.12 ms, should receive cardiac resynchronization therapy unless contraindicated. (Level of Evidence: A)

12. Addition of an aldosterone antagonist is reasonable in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be less than or equal to 2.5 mg/dL in men or less than or equal to 2.0 mg/dL in women and potassium should be less than 5.0 mEq/L. Under circumstances where monitoring for hyperkalemia or renal dysfunction is not anticipated to be feasible, the risks may outweigh the benefits of aldosterone antagonists. (Level of Evidence: B)

Class IIa
1. Angiotensin II receptor blockers are reasonable to use as alternatives to ACEIs as first-line therapy for patients with mild to moderate HF and reduced LVEF, especially for patients already taking ARBs for other indications. (Level of Evidence: A)

2. Digitalis can be beneficial in patients with current or prior symptoms of HF and reduced LVEF to decrease hospitalizations for HF. (Level of Evidence: B)

3. The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACEI and beta-blocker for symptomatic HF and who have persistent symptoms. (Level of Evidence: A)

4. Placement of an implantable cardioverter-defibrillator is reasonable in patients with LVEF of 30% to 35% of any origin with NYHA functional class II or III symptoms who are taking chronic optimal medical therapy and who have reasonable expectation of survival with good functional status of more than 1 year. (Level of Evidence: B)

Class IIb
1. A combination of hydralazine and a nitrate might be reasonable in patients with current or prior symptoms of HF and reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency. (Level of Evidence: C)

2. The addition of an ARB may be considered in persistently symptomatic patients with reduced LVEF who are already being treated with conventional therapy. (Level of Evidence: B)

Class III
1. Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: C)

2. Calcium channel blocking drugs are not indicated as routine treatment for HF in patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: A)

3. Long-term use of an infusion of a positive inotropic drug may be harmful and is not recommended for patients with current or prior symptoms of HF and reduced LVEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment (Stage D). (Level of Evidence: C)

4. Use of nutritional supplements as treatment for HF is not indicated in patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: C)

5. Hormonal therapies other than to replete deficiencies are not recommended and may be harmful to patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: C)}}

==ACC / AHA Guidelines- Patients with HF and Normal LVEF (DO NOT EDIT) == {{cquote|

Class I
1. Physicians should control systolic and diastolic hypertension in patients with HF and normal LVEF, in accordance with published guidelines. (Level of Evidence: A)

2. Physicians should control ventricular rate in patients with HF and normal LVEF and atrial fibrillation. (Level of Evidence: C)

3. Physicians should use diuretics to control pulmonary congestion and peripheral edema in patients with HF and normal LVEF. (Level of Evidence: C)

Class IIa
1. Coronary revascularization is reasonable in patients with HF and normal LVEF and coronary artery disease in whom symptomatic or demonstrable myocardial ischemia is judged to be having an adverse effect on cardiac function. (Level of Evidence: C)

Class IIb
1. Restoration and maintenance of sinus rhythm in patients with atrial fibrillation and HF and normal LVEF might be useful to improve symptoms. (Level of Evidence: C)

2. The use of beta-adrenergic blocking agents, ACEIs, ARBs, or calcium antagonists in patients with HF and normal LVEF and controlled hypertension might be effective to minimize symptoms of HF. (Level of Evidence: C)

3. The usefulness of digitalis to minimize symptoms of HF in patients with HF and normal LVEF is not well established. (Level of Evidence: C)}}