Congestive heart failure acute pharmacotherapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Acute Pharmacotherapy
The goals of acute pharmacotherapy include:
- Reduce preload
- Reduce afterload
- Reduce intravascular volume
- Improve cardiac contractility
The following acute therapies are used in the acute management of heart failure and their mechanism of action are as follows
- Diuretics reduces preload and reduces intravascular volume
- Nitroprusside reduces afterload and reduces preload
- Nesiritide reduces afterload and reduces preload
- Milrinone increases contractility and reduces afterload
- Dobutamine increases contractility in reduces afterload
- Dopamine increases blood pressure and increases renal perfusion at low doses
- Nitroglycerine reduces afterload and reduces preload
Chronic Pharmacotherapy
Diuretics
- Provide symptomatic relief
- Slows the progression of ventricular remodeling by reducing ventricular filling pressure and wall stress
- No survival benefit and may cause azotemia, hypokalemia, metabolic alkalosis and elevation of neurohormones.
- Although thiazide diuretics are effective in mild heart failure they are usually inadequate for the treatment of severe heart failure.
- Thiazide diuretics have also been associative with hyponatremia.
- Fluid retention usually responds best to furosemide (Lasix) and at doses of 10 to 20 mg per day. The patient should be told to return to their physician in the next three to seven days for further assessment including assessment of their potassium concentration. Weight loss should not exceed 1 to 2 pounds/day.
- Higher lasix doses are associated with higher mortality, likely as a surrogate of disease severity rather than part of a causal pathway.
- If there is no response to the initial dose then it can be increased by at least 50%. The maintenance dose of the diuretics lower than that required to initiate diuresis.
- If the patient gains more than two pounds and they are instructed to double the dose of their loop diuretic.
- Once the baseline weight has been re-established than they can resume their previous status.
- Intermittent use of metolazone into dose of 2.5 or 5 mg can be given if the patient is refractory to furosemide Lasix. Metolazone should be given in the inpatient setting.
- The role of potassium sparing diuretics such as spironolactone (Aldactone), amiloride, or triamterene remains the subject of controversy. Spironolactone is currently recommended as third line therapy for congestive heart failure.
- Extreme caution is necessary when adding a potassium sparing agent to the regiment that includes ACE inhibitors particularly when diabetes or renal disease is present because the patient can become hyperkalemic.
Electrolyte replacement
- ACE inhibitors reduce potassium excretion, but most patients with good renal function require potassium supplementation during daily therapy with the diuretics such as furosemide (Lasix) despite of ACE inhibitors therapy.
- Dietary supplementation is rarely adequate.
- Hypokalemia can aggravate arrhythmias and precipitate muscle cramps.
- Potassium levels >6 (particularly when occurs rapidly) can be associated with reduced myocardial contractility.
- Patients are actually at higher risk of hyperkalemia and hypokalemia. The goal is to maintain a potassium between 3.8 and 4.5 mEq.
- Unless the hypokalemia is very severe and at life-threatening level, potassium should be replaced by oral administration.
- Potassium should not be administered intravenously at a rate that exceeds 10 mEq per hour.
- Patients who use diuretics usually require approximately 20-60 mEq/day of oral potassium.
- Extra potassium should be given after the patient has noted diuresis or weight change. If patient has lost more than two pounds, the electrolyte's level should be checked every three days.
Loop Diuretics
- Agents in this class include Furosemide or lasix, bumetanide, ethacrynic acid and torsemide.
- Inhibit the Na+/K+/Cl- transporter.
- Furosemide IV reduces preload
- Relax pre-contracted pulmonary venules and thereby reduce the symptoms of pulmonary edema
Thiazide Diuretics
- Inhibit the Na+/Cl- co transporter in the distal convoluted tube.
- Recommended for management of mild chronic heart failure.
Potassium Sparing Diuretics
- Spironolactone, amiloride and triamterene.
- Inhibit principal cells in the distal convoluted tubule and cortical collecting duct.
- Inhibits Na reabsorbtion and Potassium secretion.
- Their significant side effect is hyperkalemia.
Renin-Angiotensin-Aldosterone Axis Inhibitors
Angiotensin converting enzyme inhibitor or ACE Inhibitors
- ACE Inhibitors (ACEI) should be considered as first-line therapy for the treatment of patients with clinical heart failure due to reduced left ventricular systolic dysfunction (LVSD), patients with asymptomatic LV dysfunction, and for patients who are at high risk for the development of heart failure due to the presence of coronary, cerebrovascular, or peripheral vascular disease.
- Treatment should not be deferred in patients with few or no symptoms because of the significant mortality benefit derived from ACEI therapy.
- Initial therapy usually consist of 12.5 mg tid of captopril, 2.5 mg bid of enalapril, or 2.5 mg daily lisinopril. The optimal dose is usually established by optimizing the dose every 4 to 6 weeks.
- ACE inhibitors are rarely adequate for the treatment of congestion without the use of diuretics.
- 5-10 % patients cannot tolerate ACE inhibitors because of cough. Cough can be a sign of elevated left-sided filling pressures. Sometimes cough will diminish with the treatment of heart failure. A
- Renal artery stenosis should be considered if there's a decline in renal function with the initiation of ACE inhibitors.
Angiotensin receptor blockers (ARB)
- * In the CHARM study candesartan reduced both hospitalization and mortality.
Aldosterone Antagonists
- Spironolactone is third line therapy for CHF
- An important side effect of spironolactone is hyperkalemia
Nitrates
- A nitrate may be added to ACE inhibitors to relieve symptoms of pulmonary edema
- The addition of a nitrate to an ACE inhibitor may improve exercised tolerance.
- The combination of hydralazine and nitrates is useful when ACE inhibitors are not well tolerated.
- Hydralazine by itself is only an arterial vasodilator and does not reduce left ventricular filling pressures to the same extent as nitrates and ACE inhibitors do. In fact when used alone it can stimulate sympathetic tone reflexively. The combination of hydralazine and nitrates has been shown to decrease mortality as well as improve the left ventricular ejection fraction and exercise capacity in patients with heart failure. However the combination of hydralazine and nitrates has been found to be less effective than ACE inhibitors.
- The major uses this combination is in those patients who are intolerant of ACE inhibitors.
Anticoagulants
- The annual incidence of systemic and pulmonary embolism in patients with heart failure is 2-5%. This is not that dissimilar from the risk of severe bleeding among patients to its anticoagulants which is 0.8-2.5% per year.
- As a result anticoagulation is not routinely recommended in the current guidelines for the treatment of heart failure. However among those patients with a atrial fibrillation, a history of emboli, or multiple intracardiac thrombi, or akinesis or dyskinesis detected on echo should be anticoagulated.
- While hospitalized, patients with CHF should receive DVT prophylaxis
Beta Blockers
- Metoprolol, Carvedilol and Bisoprolol have FDA approved labeling for use in congestive heart failure.
- Blockade of compensatory sympathetic stimulation is associated with arrhythmic, ischemic, remodeling, and apoptotic benefits.
- Used as monotherapy or combined with conventional heart failure management, beta-blockers reduce the combined risk of morbidity and mortality.
- Initiate low starting dosing and titrate up to tolerated target doses.
- Lopressor should be used instead of atenolol in the patient with CHF
Antiarrhythmic Drugs
Antiarrhythmic therapy should be considered as a therapy to prevent sudden cardiac death. Over 50% of heart failure patients will have asymptomatic non-sustained ventricular tachycardia and there is no general indication for treatment of this arrhythmia. T here are multiple causes of the for sudden cardiac death in the patient with congestive heart failure which include not only arrhythmic causes, but also thrombotic and other causes:
- Arrhythmic causes
- Thrombotic causes:
- Other causes:
Metabolism of Antiarrhythmics in the setting of Congestive Heart Failure
Metabolisms of following anti-arrhythmic drugs are significantly affected in patients with congestive heart failure and care should be taken regarding their administration:
- Quinidine
- Procainamide
- Disopyramide: Contraindicated in patients with heart failure.
- Moricizine
- Lidocaine
- Mexiletine
- Tocainide
- Flecainide
- Propafenone
- Amiodarone
Patients with congestive heart failure should not be treated with dronedarone.
Positive Inotropics
- Agents that increase intracellular cAMP
- Alpha-adrenergic agonists
- Phosphodiesterase inhibitors
- Agents that affect sarcolemmal ion pumps/channels
- Agents that modulate intracellular calcium mechanisms by either:
- Release of sarcoplasmic reticulum calcium (IP3)
- Increased sensitization of the contractile proteins to calcium
- Drugs having multiple mechanisms of action
- Pimobendan
- Vesnarinone
Digoxin
- Inhibits Na,K+-ATPase resulting in an increase in intracellular Na+, extracellular Ca2+ exchange increasing the velocity and extent of sarcomere shortening.
- ACC/AHA recommend digoxin for symptomatic patients with left ventricular systolic dysfunction.
- Commonly used in patients with heart failure and atrial fibrillation to reduce the ventricular response rate.
- Mortality has not been shown to be improved with use of digoxin, but the use of digoxin has been associated with a reduction in hospitalization in the RALES study.
- There is no need to load a CHF patient with digoxin. For the majority of patients with normal renal function, a daily dose of 0.25 mg of digoxin is usually adequate. In the older patient or in those patients with renal impairment, a dose of 0.125 mg per day may be adequate.
- Drugs that increase the concentration of digoxin include antibiotics and anticholinergic agents as well as amiodarone, quinidine and verapamil.
- In the RALES study, a level of < 1 ng/ml was associated with efficacy. Levels above 1 ng/ml were not associated with greater efficacy and were associated with higher mortality.
Dobutamine
- Activates beta-1 receptors resulting in enhanced cardiac contractility.
- Long-term dobutamine infusions are arrhythmogenic and increase mortality.
- Dobutamine also slightly reduces afterload
Dopamine
- Unique dose dependent mechanism of action.
- At low doses: (≤2 µg/kg/min), selective dilation of splanchnic and renal arterial beds. assists in increasing renal perfusion.
- At intermediate doses: (2 to 10 µg/kg/min), increased norepinephrine secretion results in increased cardiac contractility, heart rate and systemic vascular resistance.
- At higher doses: (5 to 20 µg/kg/min), direct alpha-adrenergic receptor stimulation increases systemic vascular resistance.
Milrinone
- Phosphodiesterase-III inhibitor that enhances cardiac contractility by increasing intracellular cyclic adenosine monophosphate (cAMP).
- Potent pulmonary vasodilator that may benefit some patients with pulmonary hypertension.
- Unlike dobutamine milrinone is beneficial in decompensated heart failure patients who are on beta-blocker therapy.
- Long term milrinone infusions are arrhythmogenic, and increase mortality.
Metformin
Ca Channel Blockers
- Although calcium channel blockers cause vasodilation their overall benefit is minimized by the fact that they have a negative inotropic effect and by the reflex activation of the sympathetic nervous system.
- These agents are not recommended as vasodilators in patients with congestive heart failure, however they may be useful as antihypertensive agents in patients with diastolic dysfunction.
Drugs to Avoid in CHF
- Dronedarone should be avoided in patients who were hospitalized with CHF (this is a boxed warning)
- Sotalol (has a negative inotropic effect)
Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
- Cardiac resynchronization therapy should only be undertaken if the blood pressure is low and if the heart failure medicines have been optimized
- CRT is indicated for symptomatic patients with NYHA III-IV heart failure and wide QRS complex (>120ms) who are him normal sinus rhythm.
- 70% of patients receiving synchronous ventricular contraction report significant symptomatic improvements.
ACC / AHA Guidelines - Recommendations for Cardiac Resynchronization Therapy in Patients with Severe Systolic Heart Failure (DO NOT EDIT)[1]
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Class I1. For patients who have LVEF less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and sinus rhythm, CRT with or without an ICD is indicated for the treatment of NYHA functional Class III or ambulatory Class IV heart failure symptoms with optimal recommended medical therapy. (Level of Evidence: A) Class IIa1. For patients who have LVEF less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and AF, CRT with or without an ICD is reasonable for the treatment of NYHA functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy. (Level of Evidence: B) 2. For patients with LVEF less than or equal to 35% with NYHA functional Class III or ambulatory Class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing, CRT is reasonable. (Level of Evidence: C) Class IIb1. For patients with LVEF less than or equal to 35% with NYHA functional Class I or II symptoms who are receiving optimal recommended medical therapy and who are undergoing implantation of a permanent pacemaker and/or ICD with anticipated frequent ventricular pacing, CRT may be considered. (Level of Evidence: C) |
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Implantation of Intracardiac Defibrillator
- 50% of heart failure patients die of sudden cardiac death.
- ICDs are indicated for patients with previous myocardial infarction and LVEF <30%, sustained ventricular tachycardia, inducible ventricular tachycardia.
- Morbidity/mortality benefit of ICD placement vs. anti-arrhythmic drug therapy is controversial.
Ultrafiltration
- Ultrafiltration has been associated with a reduced incidence of hospitalization compared with diuretics in the UNLOAD trial. There was no difference in mortality.
- The process of ultrafiltration consists of the production of plasma water from whole blood across a semipermeable membrane (hemofilter) in response to a transmembrane pressure gradient. Possible benefits of ultrafiltration include:
- Provides fluid regulation
- Relieve pulmonary edema
- Reduce ascites and/or peripheral edema
- Hemodynamic stabilization
- Improve oxygenation
- Facilitates blood product replacement without excess volume
- Enable parenteral nutritional support without excess volume
- Improves solute regulation
- Correct acid-base balance
- Correct serum sodium content
- Eliminate myocardial depressant factors or known toxins
- Correct uremia
- Correct hyperkalemia
- Correct other electrolyte disturbances
- Helps to establish homeostasis
- Reset water omostat
- Restore diuretic responsiveness
- Reduce neurohormonal activation
Cardiac Surgery
- Resection of non-viable myocardium or aneurymectoymay be an option to improve left ventricular geometry
- Revascularization without resection of non-viable myocardium may be helpful if there is hibernating myocardium
Left Ventricular Assist Devices (LVADs)
- LVADs are temporary devices to bridge end stage patients to cardiac transplantation.
- The use of LVADs as a destination device rather than as a bridge is investigational at present
Cardiac Transplantation
- Cardiac transplantation is reserved for patients with end-stage congestive heart failure despite all interventions.
- AHA/ACC Guidelines: Indications for heart transplantation:
- Any hemodynamic compromise due to heart failure.
- Requiring IV inotropic support to maintain adequate organ perfusion.
- Peak Vo2 <10 ml/kg/min.
- NYHA Class IV symptoms not amenable to any other intervention.
- Recurrence of symptomatic ventricular arrhythmias refractory to all therapeutic intervention.
- AHA/ACC Guidelines: Indications for heart transplantation:
- 80% 1 year survival, and 60% 5 year survival.
- Lifelong immunosuppressive therapy to prevent (or postpone) rejection, increased risk for opportunistic infections and malignancies.
Invasive Monitoring
- Based upon the results of the ESCAPE trial, there is no benefit in clinical outcomes with the use of a pulmonary artery line in patients with decompensated CHF.
Obstructive Sleep Apnea in the Patient with CHF
- Central sleep apnea in the patient with CHF is due to the compensatory respiratory alkalosis that is present in the patient with CHF and tachypnea
Exercise and Daily Activities
- Patient should have uninterrupted exercise at least four days a week including a walking program.
- Patients with heart failure should avoid weightlifting which increases afterload.
- The patient should not routinely lift more than 20 pounds, again which may increase afterload.
- Patients can continue their sexual activity. Some patients take 2.5 or 5.0 mg of sublingual nitroglycerine before sexual activity.
References
- ↑ Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW (2008). "ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons". Circulation. 117 (21): e350–408. doi:10.1161/CIRCUALTIONAHA.108.189742. PMID 18483207. Retrieved 2011-01-15. Unknown parameter
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