Heart Failure with Reduced Ejection Fraction
Today we will be starting a two article series on congestive heart failure. Today’s topic will be on heart failure with reduced ejection fraction (HFrEF), formerly known as systolic heart failure.
Heart failure can also be characterized by left-sided or right-sided heart failure, where clinical symptoms can be helpful in the diagnosis. In left-sided heart failure orthopnea, rales, shortness of breath, dyspnea on exertion, paroxysmal nocturnal dyspnea, and at S3 on examination may be present. Whereas with right-sided heart failure hepatosplenomegaly, JVD, peripheral edema, and dyspnea on exertion may be finding on history and physical examination.
The timely diagnosis of heart failure is crucial due to the overall poor prognosis of the disease. One month after diagnosis the survival rate is 89.6 percent, one year after diagnosis the rate is 78 percent, and five years after diagnosis the survival rate is 57.7 percent.2
Diagnosing Heart Failure
The diagnosis of CHF is still under debate, but it remains a clinical diagnosis. There are several published lists of diagnostic criteria, but the Framingham criteria are widely accepted. Studies showed that the Framingham criteria has high sensitivity for the diagnosis of HFrEF and HFpEF (heart failure with preserved ejection fraction, diastolic heart failure) at 97 percent and 89 percent respectively. These criteria are often not used to make the diagnosis; however, they are primarily used to rule out the diagnosis instead.2
The diagnosis of heart failure, whether with reduced or preserved ejection fraction, is most widely accepted by evaluating the cardiac function with an echocardiogram. This diagnostic study allows for the calculation of the left ventricular ejection fraction (LVEF) which aids in the classification of disease.
If a patient has chest pain, the American Heart Association and American College of Cardiology recommend undergoing cardiac catheterization due to it showing improved survival rates, and it can also give us the diagnosis of heart failure simultaneously. It also will allow for the assessment to see if there is coronary artery disease present, which is the etiology of HFrEF in over 66 percent of cases.2
Some other testing and diagnostic studies that can be completed initially include a chest radiograph, EKG, pro-BNP, CMP, CBC, TSH, troponin, CKMB, and urinalysis. Some other tests to consider for alternative causes of CHF are arterial blood gases, HIV screen, blood cultures, Lyme antibodies, thiamine level, and iron studies.2
Pharmacologic Therapy For HFrEF
Next, we will begin to go over the medication options for outpatient treatment of heart failure with reduced ejection fraction. Treatment will often be based on the symptoms that the patient is having. This is often characterized by using the New York Heart Association system.
The initial medication to be started in patients with HFrEF is an ACE inhibitor. Since the 1980’s ACE inhibitors have been a major treatment option for cases of heart failure in those without contraindications. The benefit that ACE inhibitors provide is class-wide and should be given to all patient with HFrEF, even those who are asymptomatic.
Angiotensin receptor blockers (ARBs) have shown benefit as well when used as a substitute for ACE inhibitors when they cannot be tolerated. They should not be given along with ACE inhibitors.
ARB/neprilysin inhibitors are a newer class of medication for the treatment of heart failure. “The inhibition of neutral endopeptidase (neprilysin) leads to increased concentrations of natriuretic and vasoactive peptides.”1 The PARADIGM-HF study showed that the medication Entresto (valsartan/sacubitril) in comparison to enalapril has decreased the rate of death (21.8 percent vs. 26.5 percent) in those on Entresto.
The difficulty with this medication is the cost. The yearly total for Entresto is around $4,600, and there is some concern that the cost of the medication might not be cost-effective for the benefit that they medicine provides.2 Another theoretical concern is that the inhibition of neprilysin could potentially increase beta-amyloid peptides that are related to Alzheimer disease; however, this has not been found to be clinically relevant at this time.1
In July 2015, the United States FDA approved the use of Entresto in HFrEF is those who have NYHA class II-IV heart failure to reduce the risk of hospitalization and death. However, since this medication is so novel, there is only one study available, and limited post-market monitoring of potential adverse effects.
Based on the information currently available, the AHA/Heart Failure Association of America guidelines recommend the use of Entresto as a first line alternative to ACE inhibitors in those with symptoms of heart failure who are not hypotensive.
Beta blockers, bisoprolol, carvedilol, and metoprolol succinate, are known to reduce mortality in patients with HFrEF when they are taken alongside an ACE inhibitor. Beta blockers work by reducing the noradrenergic influences on the heart and have a long-term benefit in patients with CHF.
Beta blockers should not be started in unstable patients or those in acute exacerbations of heart failure. However, they should be started when a patient is stable and has no symptoms at rest. Dosing for beta blockers is essential in HFrEF as appropriate amounts are listed in the table below. Dosages below the recommended target do not provide the same benefit in HFrEF patients.
Aldosterone antagonist, eplerenone, and spironolactone have been shown to be beneficial in the patient with heart failure when taken with an ACE inhibitor and beta blocker. Aldosterone antagonists have been approved for the use in all patients with HFrEF that are symptomatic, and in those three to fourteen days post myocardial infarction with symptomatic reduced LVEF.
Direct acting vasodilator isosorbide dinitrate/hydralazine can be used in patients who cannot take ACE inhibitors or ARBs primarily because of severe kidney disease. It is also indicated as an adjunctive therapy in African American patients who have persistent symptoms with ACE inhibitor therapy, due to it being seen to reduce mortality in this subset of patients.
Digoxin should be considered in patients who continue to have symptoms despite therapy with ACE inhibitor, beta blocker, and aldosterone antagonists. Digoxin primarily works as a positive inotrope in patients with heart failure. Trials have shown that digoxin does not affect the mortality rate of patients with HFrEF, but it does decrease the rate of hospitalizations.
Ivabradine is a sinus node modulator that some studies have shown to reduce the rate of death associated with CHF and decompensated heart failure by 18 percent in patients with a heart rate over 70 beats per minute. The same study showed no benefit in patients with a lower heart rate. Another trial, however, showed no improvement in hospitalization rates, or risk of death with Ivabradine. Due to this inconsistency, the AHA notes that Ivabradine may be considered in individual patients, but beta blockers should be used first line.1
Loop and thiazide diuretics can be used to aid in volume control in patients with HFrEF; however, they do not provide any benefit on the mortality rate associated with heart failure. Therefore, they should only be used to treat fluid congestion.
As mentioned previously, a vast majority of patients with heart failure with reduced ejection fraction have underlying coronary artery disease as their predisposing etiology. In these cases, statins should be instituted. There is some gray area, however, due to the fact that two large trials showed no benefit from the addition of a statin in patients with HFrEF with underlying coronary artery disease.1
Implantable cardioverter-defibrillators improve mortality, and cardiac resynchronization therapy can aid in symptom relief of patients with heart failure. Patients who have a severely reduced ejection fraction whose life expectancy is over one year can be referred for evaluation for possible device placement by electrophysiology.
A final thing to remember is that medications do work very well for the treatment of HFrEF, but some lifestyle changes can be made as well. Improving aerobic exercise activity, as well as reducing salt intake to less than 2 grams daily and reducing fluid intake to less than 2 liters total daily can aid in the reduction of fluid retention in patients with heart failure.
- Am Fam Physician. Heart Failure Due to Reduced Ejection Fraction: Medication Management. 2017;95(1):13-20. Copyright © 2017 American Academy of Family Physicians.
- Am Fam Physician. Diagnosis and Evaluation of Heart Failure. 2012;85(12):1161-1168. Copyright © 2012 American Academy of Family Physicians.
- UpToDate. Clinical manifestations and diagnosis of heart failure with preserved ejection fraction. Accessed: 6/9/2018.
This article, blog, or podcast should not be used in any legal capacity whatsoever, including but not limited to establishing standard of care in a legal sense or as a basis of expert witness testimony. No guarantee is given regarding the accuracy of any statements or opinions made on the podcast or blog.