Introduction – Heart Failure with Reduced Ejection Fraction
Heart Failure with Reduced Ejection Fraction (HFrEF) is a common condition, with higher incidence and prevalence at later stages of life. The underlying cause is found in some form of injury or disease of the heart. It is estimated that about 2% of the population is affected and in individuals over 80 years the prevalence is 10%.
Heart failure has a high mortality rate, which can be reduced with adequate treatment. Sudden death is a common cause of mortality. Heart failure can debut acutely (acute heart failure), but can just as often have an insidious onset. Registry studies show that a remarkable number of patients are not adequately diagnosed or treated according to established recommendations. In part, this may be because the symptoms can easily be mistaken for other causes or because heart failure is often one of several comorbidities of the patient.
Treatment – Heart Failure with Reduced Ejection Fraction
Evaluate what caused or worsened the heart failure. Treatment for the underlying cause is very important. For example, in the case of valvulopathies, surgical measures must be considered. For atrial fibrillation, electrical rhythm conversion should be considered.
Treatment for the underlying disease is combined with heart failure treatment as indicated below. The insertion of ACE inhibitors and beta-blockers is best done with the assistance of a heart failure clinic that allows frequent follow-up visits. The latest version of the European Cardiologists Association’s Guidelines for Heart Failure (2016) presents a flow chart that can aid therapy choice for patients with heart failure and impaired systolic function.
- Furosemide (Furix) is given in fluid retention. After eventual intravenous treatment, continued maintenance therapy is administered through pills, 20-160 mg daily. Once the excess fluid has been resolved, one should try to lower the dose of diuretics to the least effective dose and preferably withdraw the treatment completely, if possible. Potassium substitution is rarely needed if ACE inhibitors are given. Diuretics are symptomatic therapy and have no proven beneficial effect on mortality.
- ACE inhibitors improve survival and should be considered in all patients with chronic HFrEF. Indication is found in lowered ejection fraction (below 40% ), with or without symptoms of heart failure. Contraindications are mainly severe renal impairment, dehydration, hyperkalemia, and severe hypotension. Start with low doses and gradually increase (usually double) each week under clinical supervision until you reach the target dose.
- Beta-blockers improve survival and should be considered in all patients with chronic heart failure (HFrEF). Three beta-blockers are indicated for heart failure treatment: Bisoprolol (Emconcor CHF), carvedilol (Kredex), Metoprolol succinate (Seloken Zoc). The indication is determined by symptoms in conjunction with lowered ejection fraction (below 40%). Patients should be in a stable condition without significant fluid retention and currently on ACE inhibitors before starting treatment. Start with low doses and gradually increase for several weeks until the planned target dose is reached. In some cases, it is possible to start with a beta-blocker before ACE inhibitors. Contraindications mainly consist of AV block, bradycardia, significant asthma, and severely unstable heart failure. Since there is a risk of transient clinical deterioration at the start of treatment, the treating physician should have experience with beta-blockers in heart failure.
- Angiotensin receptor blockers (ARBs) are an alternative to patients who do not tolerate cough as a side effect – like in therapy with ACE inhibitors. Some well-proven ARBs in heart failure are candesartan (Atacand) and valsartan (Diovan). Generic losartan has also been studied in heart failure, but higher doses than previously indicated are needed to achieve the full effect: 100-150 mg daily.
- Mineral corticoid receptor antagonists (MRAs): Low-dose spironolactone (Aldactone) (12.5-50 mg daily), in combination with ACE inhibitors, has been shown to have a mortality benefit in NYHA III-IV class patients. Eplerenone (Inspra) treatment has shown additional positive effects in managing heart failure after myocardial infarction and has also shown good efficacy in mild heart failure (NYHA II).
Eplerenone lacks the endocrine side effects of spironolactone. The dose of eplerenone is 25-50 mg daily. Today’s treatment recommendation is that the majority of patients with heart failure receive treatment with ACE inhibitors (alternatively ARB) + beta blockers + MRA.
Note that all potassium-sparing diuretics combined with ACE inhibitors or ARBs increase the risk of hyperkalemia and a rise in creatinine. Potassium must always be monitored during the insertion of MRA, at dose increase and also at follow-ups. Concurrent treatment with ACE inhibitors + ARB + MRA is not recommended because of the increased risk of side effects.
- RAAS blockade and kidney function: ACE inhibitors, ARB and MRA can all cause a creatinine and potassium increase. Generally, an increase in creatinine of 30-50% from baseline is acceptable, up to a maximum of 250 μmol / L (or eGFR 25 mL/min). A potassium increase up to 5.5 mmol/L can also be accepted. The risk of kidney damage and hypotension increases with aggressive diuretic therapy and dehydration. Patients with RAAS blockade should be informed to temporarily discontinue medication if they experience unexpected dehydration (eg diarrhea and vomiting). Despite the creatinine increase, the positive effects of RAAS blockade are not adversely affected compared to situations where creatinine is unaffected.
- In patients with persistent elevated resting heart rate (> 75 beats per minute), despite the recommended dose of beta-blockers is administered, a sinus node inhibitor, ivabradine (Procoralan) can be used if the patient is in sinus rhythm. The dosage is 5-7.5 mg x 2.
- A new combination drug (angiotensin receptor neprilysin inhibitor = ARNI), has been shown to be more effective than ACE inhibitors alone. Sacubitril- valsartan (Entresto) reduces the degradation of natriuretic peptides such as BNP, thus increasing the pharmacological effects of these proteins. Entresto may be considered in case of insufficient effect of standard medical treatment. The drug then replaces ACE inhibitors/ARB, which must have been discontinued 36 hours before insertion of the new therapy. The dosage is (24/26) 49/51 – 97/103 mg x 2 daily. As the diuresis tends to increase, one should be observant of electrolyte changes and possibly reduce doses of the diuretics.
- In addition to medical treatment, pacemakers with stimulation in both cardiac chambers (biventricular pacing or resynchronization called CRT, cardiac resynchronization therapy ) have shown good results. The patients in question are suffering from persistent symptoms (NYHA class II-IV) despite adequate medical treatment, ejection fraction <35%, and widened QRS complexes (> 130 msec). Such pacemakers can also be provided with defibrillator function (ICD) in some cases. It has also been shown that ICD reduces the risk of sudden death in poor ventricular function and may be indicated, even without previously demonstrated arrhythmias.
- Digoxin has a narrow therapeutic window and the risk of overdose with arrhythmias as the most serious side effect. The indication is mainly atrial fibrillation in combination with heart failure. Low doses are recommended and serum concentration should be monitored (0.6-1.1 nmol/L).
- Intravenous iron therapy: Patients with heart failure sometimes have low iron levels, possibly due to poor bowel resorption or other partially unclear causes. One study has shown good symptom relief with increased quality of life in patients with documented iron deficiency. The indication exists if together with Hb <150 g / L, serum ferritin <100 ng / mL, or between 100 and 300 ng / mL, if transferrin saturation (TSAT) <20%.
Intravenous iron is given in the form of iron carboxymaltose (Ferinject) at a suitable dose according to iron levels and body weight, usually 500-1000 mg by intravenous injection. The dose can be repeated until the iron levels are normalized. In the CONFIRM-HF study, the median dose was 1500 mg over the course of one year. Intravenous iron can cause severe allergic reactions, including anaphylaxis, and patients with other allergies are at increased risk. Preparedness for allergic reactions should, therefore, be of high importance during administration.
- For those patients who cannot be adequately treated by the above methods, heart transplantation may be considered, sometimes preceded by insertion of a mechanical heart pump for a shorter or longer period of time.
- Patients with unilateral right heart failure may have pulmonary hypertension or pulmonary embolism
Further care – Heart Failure with Reduced Ejection Fraction
- Complete the assessment and decide on treatment of the underlying cause.
- Chronic heart failure is usually lifelong and requires regular follow-ups. In most cases, treatment must be reassessed in case of deterioration.
- Instruct the patient to check for intrinsic symptoms (shortness of breath, edema, daily weighing) and prescribe caution with salt and high liquid intake. Smoking cessation and caution with alcohol is recommended.
- Initial care after longer inpatient visits is best done at a dedicated nursing-based heart failure clinic. Such a unit can also convey information and provide education about heart failure to the patient and relatives.
- Rehabilitation through physical therapy-guided exercise programs improves patient mobility, symptoms, and quality of life.
- Cardiac ischemia (angina pectoris, MI) without heart failure
- Pulmonary diseases, COPD, asthma
- Pulmonary embolism
- Renal or liver failure with edema
- Peripheral causes of edema
- Anemia and/or bleeding
- Ponikowski P, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-200.
- Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 2015;36:657-68.